What are the reason for Cracks on the road

Thankshttps://www.rhino-uk.com/

There are numerous factors influencing the performance of a pavement, the following five are considered the most influential (Transportation research board, England; April 1985)

 1)Traffic

 Traffic is the most important factor affecting pavement performance. The performance of pavements is mostly affected by the loading scale, arrangement and the number of load repetitions. The damage caused per pass to a pavement by an axle is defined relative to the damage per pass of a standard axle load, which is defined as a 80 kN single axle load (E80). Thus a pavement is designed to withstand a certain number of standard axle load repetitions that will result in a certain terminal condition of deterioration.(Kamal M.A. et al., 2009)

2) Moisture

Moisture significantly reduces the supporting ability of gravel materials, especially the sub grade. Moisture enters the pavement structure through capillary action. The resulting action is the wet surface of particles, excessive movement of particles and dislodgment which ultimately results in pavement failures. (Terrel 1990)

3)Sub grade

The sub grade is the lower layer of soil that supports the wheel loads. If the sub grade is not strong enough the pavement will show flexibility and finally the pavement will fail. Pavement will fail to perform ideally if the variation in particles behavior is not catered for in the design.

4)Construction quality

Pavement performance is affected by poor quality construction, inaccurate pavement thicknesses, and adverse moisture conditions. These conditions stress the need for skilled staff and the importance of good inspection and quality control procedures during construction.

Causes of cracking in road surfaces: Cracks in the highway emanate from either:

 1.The surface, where traffic induced fatigue, thermal movement and warping stress will initiate cracking
2.The sub-base, where seasonal expansion and contraction of the pavement causes reflective cracking

The sort of cracks that can be treated are:

      • reflective cracks
      • surface generated cracks
      • shrinkage cracks
      • longitudinal lane joints
      • concrete spalling
      • asphalt/concrete interface joints
      • mid bay cracking
Cracks generated from the surface are caused by fatigue from traffic, especially HGVs. These types of cracks when excavated, will often not show further cracking in the layers below the surface course.
Cracks generated from movement in the sub-base are called reflective cracks and will show through in the wearing course because movement in the underlying layers is being mirrored in the top surface. Traditional asphalt road surfaces, whilst being called ‘flexible’ roads when compared to concrete ones, are not able to contain concentrations of such high movement.

Why is this movement taking place? This all depends on the structure of the road. Traditionally roads are built in layers and these layers are designed to bear the load of traffic in varying degrees. Many roads have concrete in those lower layers. As temperatures change, road surfaces (like other materials) expand and contract. Concrete is designed in slabs and designed to focus this movement at the joint between slabs. Lean mix and continually reinforced concrete also focuses movement in concentrated points. Asphalt reacts differently to temperature changes, expanding and contracting evenly over the entire surface area.

This incompatibility of the concrete and asphalt to react similarly, leads to asphalt overlays cracking when laid on top of concrete sub-bases.
Couple this with variations in which the different layers of the road surface heat up from the sun, the lower layers expand at a slower rate to the surface ones, and it is no wonder that a road surface cracks as it does.
What is important to consider is that in most cases, a substantial crack in the road surface is likely to be in a position where movement is the cause. Repair methods should consider materials with the flexibility to accommodate that movement when it occurs again in the future.

How estradiol/progesterone participate in cognitive function in women

Thanks ;Castalia Francon
An Interesting Study Reveals how the Hippocampus/Cortex Work Together

Sex Differences? Of Course
Women use spatial navigation just before their periods, but rely more on cues from their surroundings during ovulation.

The present study shows that menstrual cycle phase influences the type of memory system that is likely to be engaged in by women when solving a task or effectively navigating a virtual environment. However, the finding of this study which deserves more focus is that Progesterone, as it varies over the monthly cycle, is found to be a key modulator of which strategy is utilized. in fact as the researchers state, their initial hypotheses, which did not take Progesterone levels sufficiently into account as being a key determinant, were proved wrong.
Different learning systems were first documented by Tolman and colleagues (1946) who showed that rats utilize different strategies to find their way in a maze . Namely, several learning strategies can be used: one is response strategy, which is a strategy that relies on body turns at specific points in the environment forming stimulus- response associations, and the second is spatial strategy, which is allocentric, i.e. independent of the position of the observer and relies on forming stimulus–stimulus associations between land- marks in order to create a cognitive map of the environment.
These systems are dissociable, they can be competitive, and rely on dif- ferent brain regions to function optimally. The hippocampus is implicated in spatial memory whereas the dorsal striatum (which includes the caudate nucleus) is crucial for response memory
Women tested in the mid/late luteal phase, when P is high, use a spatial strategy significantly more than a response strategy. In contrast, during the early follicular (low E2 and P) and ovulatory (high E2) phases, response strategy was used more fre- quently
Thus, these results do NOT support our hypothesis that a high E2 state would be associated with spa tial strategy use and a low E2 state with higher proportion of response strategy use, BUT they suggest that multiple memory system bias in cycling women is mediated by changes in P such that response memory is promoted when P is low, and spatial memory is enhanced in the phase of the cycle that is characterized by high P levels.
The mid/late luteal phase, when P is high, is associated with a significant increase of spatial strategy. Conversely, a response strategy is used in the early follicular and ovulatory phase, when P is low. Thus, it would appear that multiple memory system bias is mediated by changes in P and, possibly, how P and E2 interact.
Consistent with other studies (Maki et al., 2002; Mordecai et al., 2008; ), here, women learned and remembered more words during the ovulatory phase, when E2 levels are high.
These findings support the growing body of research showing that cognitive func- tion is modulated by and change with fluctuating hormones across the menstrual cycle.
It has been consistently shown in rodents that estrogen impacts multiple memory system bias such that low estradiol (E2) is associated with increased use of a striatal-mediated response strategy whereas high E2 increases use of a hippocampal-dependent spatial memory.
It has been observed that E2 is associ- ated with changes in cognition in women; for example, E2 has been linked with improved verbal memory whereas it is associated with impaired performance on mental rotation tasks Hippocampal volume changes across the menstrual cycle in women, i.e., high endogenous E2 levels are asso- ciated with an increase in hippocampal grey matter
In addition, it has previously been found that estrogen receptors are present in the human hippocampus . Thus, E2 could be structurally altering the hippocampus and binding to estrogen receptors within this brain area to promote spatial memory.
Progesterone (P) has been shown to be associated with both enhanced and disrupting (Freeman et al., 1992) effects on verbal memory in women. It is important to note that the majority of studies that are focused on hormones and cognition in women, are carried out with a post- menopausal sample, taking hormone replacements.
These samples of women typically receive progestin with their hormone treat- ments that include E2, thus, very few studies have focused on the effects of P in isolation. P has been shown to increase hippocampal spine density when administered with E2, but these spine den- sities decrease more rapidly than when E2 is administered alone
P receptor function is dependent on induction of E2 receptors (Lydon et al., 1995), which suggests that many of the effects linked to P are also underscored by E2 action. Furthermore, E2 and P are often studied separately so the interac- tion between the two hormones, and how this can potentially affect cognitive function, is not well understood. E2 and P seem to work in concert to affect hippocampal function and, possibly, multiple memory system bias.
Participants were split into either an early follicular (i.e., when E2 levels are low), ovulatory (i.e., when E2 levels are high) or mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) phase group, using self-reported date of the menstrual cycle. Serum hormone level measurements (E2, progesterone, testosterone) were used to confirm cycle phase assignment.
NOTE: Recall that Estradiol peaks towards the end of the follicular phase (ovulation) and then rises and plateaus across the luteal phase. The menstrual cycle is also marked by changes in P levels such that they are low throughout the follic- ular phase while they peak and plateau in the luteal phase, before dropping at the onset of menstruation (for review, see Ref.: Hussain et al., 2014; Mihm et al., 2011). E2 levels are higher in the ovulatory phase compared to the early follicular phase, which is marked by low E2 levels throughout menstruation
We used a virtual navigation task. Basically, it was like a video game where women had to find their way through a maze. The maze can be completed either by using the cues in one’s surroundings and making a mental (cognitive) map of the area, or by remembering where each maze arm is relative to another, for example noting that you have to skip two arms then take the next arm. Later we remove the surrounding cues and see how well or poorly someone completing the maze does. This allows us to test which memory system they preferentially use.
Participants were administered a verbal memory task as well as a virtual navigation task that can be solved by using either a response or spatial strategy. Women tested in the ovulatory phase, under high E2 conditions, performed better on a verbal memory task than women tested during the other phases of the cycle
We found that during the ovulatory phase when estrogen peaks, women tend to use response memory to solve the maze. Asked to navigate a virtual maze, most women who are ovulating (i.e., when E2 levels are high) will rely on response memory, using cues from their surroundings to memorize turns.
Response memory is like basic habitual motor memory, such as turning right then left to get to work. However, when women are in the mid/late luteal phase of the cycle, just prior to menstruation when progesterone peaks and estrogen also rises again, they are more likely to use spatial memory.
Women in the premenstrual phase of their cycle, however, relied on spatial memory, picturing an aerial map of the maze in their heads.
Interestingly, women tested in the mid/late luteal phase mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) when progesterone is high, predominantly used a spatial strategy, whereas the opposite pattern was observed in the early follicular and ovulatory groups
Spatial memory is what you’d use if you encountered a roadblock on your way to work, and had to mentally pull up a map of the neighborhood to think of an alternate rout
An interesting set of observations here, but we suspect that they might be more strongly phrased in terms of the details and mechanisms of hippocampal/cortical partnering in regard to the two different situations. In other words it is our belief that it would indicate more to state that the landmarks..and so called "response" strategy were dependent on cued recall by the women and thus reliant on the arisal of verbal or other indices via a process akin to "episodic memory recall". This would go hand in hand with the performance on the verbal recall test, as well.
What is more problematic to us is that the researchers do not have a suficiently articulated or sophisticated view of just how it is that the hippocampus works in tandem with other systems to aid in both navigation and in episodic memory.
The 'response" strategy is not sufficiently appreciated as depending upon much more than some merely "procedural" movement control function. The "responses" in that strategy depend on a back and forth dialogue with 'episodically" based neuronal ensembles in the hippocampal area that are accessible via verbal and cortical efforts....and to which priority is given by the user. On the contrary the spatial strategy is one where the user has faith in the mapping and the abstract spatial configurations implied by the geometry of the "map" being relied upon.
It is truly frequently disheartening to watch neuroscience researchers seemingly lost in a maze of their own when trying to speak coherently and usefully about how the hippocampus works. The segmentation of hippocampal function into some truly insipid aspect such as "verbal memory" that is apart and not ever articulated in terms of how it related to the other more well known functioning of the hippocampus in spatial navigation is truly an egregious omission...and the researchers deserve to be befuddled by their own data.
Clearly both these aspects of the hippocampus, verbal recall and navigation, MUST have something to do with each other. Yet they are treated as if they are too randomly placed items on a supermarket shelf to be selected by the researcher shopping for a research project. g
The verbal recall testing was enhanced during high Estradiol times of month...so you would think that the question of the potential inverse relation between performance on the two types of tests would be even briefly considered by the researchers. But alas they don't get very far at all. In fact they flounder in their discussion through a variety of statisfical and other more superficial factors as causing their unexpected results, rather than focus on better DEFINING just how it might be that the hippocampus does its job..or jobs.
One of the points they do raise, to their credit, but only in passing is that It has been shown that hormonal changes across the cycle are also related with changes in lateraliza- tion during completion of a verbal task, such that lateralization is pronounced when E2 levels are low.
This should reasonably raise the notion that the hippocampus, too, has a left and right part, and that episodic memory as measured by verbal recall (as badly as that is defined) tends to depend on the left hippocampal areas and that the female hormone mix might indeed tend to lead to less "lateralization" within the hippocampus as well...and thus recruit both of its aspects in task performance? Sounds reasonable to us..but this is not discussed.
Additionally of the problem here is the surprise that Progesterone plays a vital function in modulating how Estradiol impacts upon the brain and the manner in which women choose to cope with events. The precedent studies were frequently based on work with rats and humans may be different from rodents in this regard. Here, both the lowest and highest E2 levels observed across the cycle were associated with response strategy use. The difference observed in how E2 impacts multiple memory system bias in rodents and in humans could be explained by the significant difference between the rat estrous cycle and the human menstrual cycle. In rats, E2 and P peak concurrently, such that a high E2 phase is also marked by high P.
Conversely, in women, the two hormones fluctuate dif- ferently and peak at different points in the cycle. It is possible that ovarian hormones interact differently in the human brain and, thus, affect cognitive functions, such as multiple memory system bias, in a unique way.
This interaction is critical in unraveling the mysteries of hormonal effect on preference of cognitive strategy and effectiveness of use, however, the absolutely incomopetent and bogus Women's Health Initiative studies of the early 2000;s along with the almost fraudulent coverup by the medical cronies of those who incompegtently conducted those studies created massive confusion not only among clinicians but among researchers as the difference betwen use of 'Progesterone" (the real thing) and various Toxic syntheic "progestagens" (formulated by big Pharma who sponsored the studies and has continued to promote the use of these toxic medications.
These "progestagens" do NOT act upon the brain and its neurosteroids and its neurotransmitters in the same way as bio identical Progesterone does..and in fact has some directly antithetical effects.
So as we read the literature search and discussions of current articles we find them totally confused, misinformed and practically incoherent in trying to reason out why they have such conflicting results on Estradiol and "progestagen" use'.. Thus, the WHI not only led to the damaging of the health of countless women but also succeeding in sabotaging the research data on the basis of which researchers such as the ones here have predicated their own research designs.
A Few comments from the Authors when Interviewed
https://www.researchgate.net/…/how-women-navigate-depends-o…
RG: What is the significance of these results?
Brake: While we have known for years that estrogen affects the brain to cause memory bias in female rodents, this is the first study to see how hormones affect women's memory.
RG: Does birth control interfere with these preferences for one memory strategy over another?
Brake: We did not test women on birth control, but I would imagine that it could affect memory bias, depending on the form and dose.
Would you recommend changes to the way studies involving memory tasks are conducted in light of your results?
I would certainly note that researchers studying memory in women or female mammals should control for hormone levels.
RG: What led you to look into the effects of hormones on memory bias?
Brake: It's about bloody time that we start understanding more about the female brain. Every mental disorder or disease, every single one, has a sex bias.
Yet, we still mostly only study the brains of men. Since researchers began studying the brain, they’ve known that studying the female brain is messy. There was more variability, which people suspect could be accounted for by changes in circulating ovarian hormones, so many people couldn't be bothered with all that extra variability in their studies.
DOI: 10.1016/j.psyneuen.2016.05.008
Aside from the likelihood of significantly misleading data that undoubtedly has been arising from various navigation studies and attempts to understand hippocampal function, we note the related issues of lesser importance but one with which we can identify: Getting around via Digital Maps and Navigational Aids:
Why Your Maps Should Get in Touch with Their Feminine Side
http://www.xyht.com/spatial-i…/maps-get-touch-feminine-side/

The way Gratitude Literally Alters The Human Heart & Molecular Structure Of The Brain

Gratitude is a funny thing. In some parts of the world, somebody who gets a clean drink of water, some food, or a worn out pair of shoes can be extremely grateful. Meanwhile, somebody else who has all the necessities they need to live can be found complaining about something. What we have today is what we once wanted before, but there is a lingering belief out there that obtaining material possessions is the key to happiness. Sure, this may be true, but that happiness is temporary. The truth is that happiness is an inside job.

It’s a matter of perspective, and in a world where we are constantly made to feel like we are lacking and always ‘wanting’ more, it can be difficult to achieve or experience actual happiness. Many of us are always looking toward external factors to experience joy and happiness when really it’s all related to internal work. This is something science is just starting to grasp as well, as shown by research coming out of UCLA’s Mindfulness Awareness Research Center. According to them:

"Having an attitude of gratitude changes the molecular structure of the brain, keeps grey matter functioning and makes us healthier and happier. When you feel happiness, the central nervous system is affected. You are more peaceful, less reactive and less resistant. Now that’s a really cool way of taking care of your well-being."

"Gratitude writing can be beneficial not just for healthy, well-adjusted individuals, but also for those who struggle with mental health concerns. In fact, it seems, practising gratitude on top of receiving psychological counselling carries greater benefits than counselling alone, even when that gratitude practice is brief" We found that across the participants when people felt more grateful, their brain activity was distinct from brain activity related to guilt and the desire to help a cause. More specifically, we found that when people who are generally more grateful gave more money to a cause, they showed greater neural sensitivity in the medial prefrontal cortex, a brain area associated with learning and decision making. This suggests that people who are more grateful are also more attentive to how they express gratitude. ">Most interestingly, when we compared those who wrote the gratitude letters with those who didn’t, the gratitude letter writers showed greater activation in the medial prefrontal cortex when they experienced gratitude in the fMRI scanner. This is striking as this effect was found three months after the letter writing began. This indicates that simply expressing gratitude may have lasting effects on the brain. While not conclusive, this finding suggests that practising gratitude may help train the brain to be more sensitive to the experience of gratitude down the line, and this could contribute to improved mental health over time.

Some Facts 

1. Gratitude unshackles us from toxic emotions

2. Gratitude helps even if you don’t share it

3. Gratitude’s benefits take time

4. Gratitude has lasting effects on the brain

Heart

“Emotional information is actually coded and modulated into these fields. By learning to shift our emotions, we are changing the information coded into the magnetic fields that are radiated by the heart, and that can impact those around us. We are fundamentally and deeply connected with each other and the planet itself.” 

“One important way the heart can speak to and influence the brain is when the heart is coherent – experiencing stable, sine-wave-like pattern in its rhythms. When the heart is coherent, the body, including the brain, begins to experience all sorts of benefits, among them, are greater mental clarity and ability, including better decision making.” 

Conclusion

Every individual’s energy affects the collective field environment. The means each person’s emotions and intentions generate an energy that affects the field. A first step in diffusing societal stress in the global field is for each of us to take personal responsibility for our own energies. We can do this by increasing our personal coherence and raising our vibratory rate, which helps us become more conscious of the thoughts, feelings, and attitudes that we are feeding the field each day. We have a choice in every moment to take to heart the significance of intentionally managing our energies. This is the free will or local freedom that can create global cohesion. – Dr Deborah Rozman, the President of Quantum Intech

Thanks; https://greatergood.berkeley.edu,http://bernardalvarez.mysharebar.com

Sai Baba Miracle- Story of Grinding Wheat

 One time, there was an epidemic of Cholera in Shirdi. Helpless Shirdi people approached Baba for relief. On this Baba after washing his hand and face took some wheat and started grinding in a hand mill. Then he asked the village people to take the flour and throw it on the village borders. With grace of Baba, from that time onward the cholera epidemic subsided and the people of the village were happy. By grinding wheat here Baba actually meant that, it was not the wheat, that was ground but cholera itself was ground to pieces and pushed out of the village.

How Phototherapy used in dermatology

Over many centuries, treatment with sunlight or "heliotherapy" was used in the treatment of skin diseases. More than 3500 years ago, ancient Egyptian and Indian healers used the ingestion of plant extracts or seeds in addition to sunlight for treating "leucoderma". Modern phototherapy began with Nobel Prize winner Niels Finsen who developed a "chemical rays" lamp with which he treated patients with skin tuberculosis. However, it took several decades until phototherapy was introduced anew into the dermatological armamentarium. It was the development of photochemotherapy (PUVA) in 1974 that marked the beginning of a huge upsurge in photo dermatology.

History of Photochemotherapy

The Indians and Egyptians in 2000 BC used the pigment-stimulating properties of the psoralen-containing Bavachee plant (Psoralea corylifolia) and Ammi majus respectively for the treatment of vitiligo. But a millennium later, in 1947, Fahmy, an Egyptian pharmacologist, could isolate psoralen compounds from Ammi majus. Parish successfully introduced a treatment combining 8-methoxypsoralen and UVA called PUVA using newly developed Henselar high intensity artificial UVA light. Topical and bath PUVA were reported as early as 1976 but did not gain as much popularity as the oral form.

Ultraviolet radiation is a small component of the electromagnetic spectrum with a narrow band of radiation from 200-400 nm. The UV spectrum is further divided into UVC (200-280 nm), UVB (280-315 nm) and UVA (315-400 nm).

Phototherapy is the therapeutic use of ultraviolet irradiation without exogenous photosensitizer. Photochemotherapy (PUVA) is the combined use of the drug psoralen and UVA radiation to achieve an effect not achieved with the individual components alone. While artificial ultraviolet radiation that allows precise dosing has only been available for the last century, the recognition of the therapeutic effect of sunlight, of which ultraviolet light comprises a proportion, goes back to ancient times.

 The subsequent development of high intensity UV sources with defined spectra facilitated an optimized therapy for psoriasis and led to an expansion of indications for photo(chemo)therapy also in combination with topical and systemic agents. The introduction of extracorporeal photo pheresis in 1987 for cutaneous T-cell lymphoma and of topical photo dynamic therapy widely expanded the therapeutic possibilities in dermato-oncology. 

Phototherapy is most frequently used to manage psoriasis. It is also helpful in the treatment of a multitude of other skin problems, including: cutaneous T-cell lymphoma, vitiligo, lichen planus, granuloma annulare, pityriasis rosea, acne, generalized itching from various causes, diseases of the hands and feet, atopic and other types of eczema.

PUVA Photochemotherapy

Psoralen plus ultraviolet A (PUVA) photochemotherapy is the photochemical interaction between psoralen and ultraviolet A (UVA) (320 to 400 nm) radiation, which has a beneficial effect in psoriasis and other skin diseases.

Psoralens

Psoralen are naturally occurring tricyclic furocoumarin compounds, present in fruits and vegetables such as limes, lemons, figs and parsnips. The derivative most widely used is 8-methoxypsoralen principally of plant origin but it is available as a synthetic drug. 4, 5, 8-trimethyl psoralen (TMP, trioxsalen) which is synthetic is less phototoxic after oral administration and is primarily used for the treatment of vitiligo.

Orally methoxsalen (8-MOP) is absorbed from the gastrointestinal tract and photosensitivity is present one hour after the dose, reaches a peak at about two hours and disappears after about eight hours. ^[2] The serum half-life of approximately one hour and is rapidly eliminated which prevents photosensitivity. ^[3] 

When applied locally 8-MOP rapidly penetrates the skin and can be detected in the urine after four hours. The plasma levels of 8-MOP in patients receiving total body topical 8-MOP are comparable to those found during oral 8-MOP ingestion. ^[4] The plasma concentration of TMP after bath treatment is only approximately 1% of the plasma after oral ingestion.

Principles of PUVA therapy

The rationale for PUVA therapy is to induce remissions of skin diseases by repeated, controlled phototoxic reactions. These reactions occur only when psoralens are photoactivated by UVA.

Sources of UVA radiation

UVA sources commonly used for PUVA therapy are fluorescent lamps or high-pressure metal halide lamps. The typical fluorescent PUVA lamp has an emission peak at 352 nm and emits approximately 0.5 percent in the UVB range. UVA dose are given in J/cm ² , usually measured with a photometer with a maximum sensitivity at 350 to 360 nm.

Treatment Protocols

PUVASOL

Psoralens with sunlight as the source of ultraviolet A-rays is known as PUVASOL. In centers where artificial chambers are not available PUVASOL is the most commonly used mode of treatment.

Here both UVA and UVB in sunlight result in photoaugmentation  and photoaddition.  A major disadvantage of solar irradiation as a light source is the difficulty in quantifying UV light. The total amount of UVA reaching the skin at any one time varies widely depending on the season, time of the day, latitude and conditions of the atmosphere. Other disadvantages are lack of privacy, difficulty in monitoring the dose of ultraviolet rays and in addition to ultraviolet A, ultraviolet B, infrared rays and visible light which are not needed for PUVA therapy may lead to undesirable effects. UVB in sunlight can increase the thickness of epidermis and this makes the sun exposed skin leathery and this may interfere with the effectiveness. Using a solarium and a PMA 120 complete privacy can be provided.  The main advantages of sunlight as a source of PUVA is that it is inexpensive and patient need not travel long distance for treatment.

Topical treatment Application of 8-MOP in creams, ointments or lotions followed by UVA irradiation is effective in limited plaque psoriasis and for palmoplantar disease. It can also be used to induce pigmentation over streaks of residual pigmentation following punch grafting and when other measures fail to induce pigmentation.

Methodology: A lotion containing 0.1 to 1% 8-MOP is applied and exposed to sunlight either immediately or after one to two hours. ^[8],[9] This treatment is given three to four times weekly with UVA dose being gradually increased. Maintenance dose may be needed.

Among the psoralens TMP is most convenient for topical application because of its weak penetrability.  The penetrated drug makes photo adducts with DNA molecules even if UVA light is given as soon as the drug is painted resulting in significant inhibition of epidermal DNA synthesis. 

Advantages of topical psoralen therapy are that systemic side effects can be avoided. The disadvantages are that topical PUVA is laborious and time-consuming, if every lesion has to be treated individually. The formation of erythema and blisters is more common with topical psoralen application and intense irregular pigmentation may be seen at the site of treated plaques.

Bath water delivery of 8-MOP and trioxsalen

Bath water psoralen delivery plus UVA has also been found to be equal to or better than local application of psoralen with ointments, creams or lotions.

Psoralen bath delivery eliminates the laborious application required with other topical modalities. The even skin distribution delivered by bath water leads to even pigmentation. Bath water delivery of 8-MOP was found to be as effective as oral administration of 8-MOP and required smaller amounts of UVA radiation and yielded fewer side effects.

Methodology: Bath solutions are prepared by diluting 50 ml of 8-MOP in 100 liters of bath water resulting in a final concentration of 3.75 mg/L. Patients soak for 15 min in this solution and then quickly wipe dry. Immediately patients are given whole body irradiation with UVA, the initial dose depending upon the skin type.

Bath-suit delivery of psoralen

In India, use of bath tub is not in vogue and water problem is perennial and most of the attending patients are poor. Hence bath suit therapy is another alternative therapy found to be an effective therapy for psoriasis. Advantages of bath-suit delivery of 8-MOP are that it requires only two liters of water and 0.8 ml of 8-MOP solution when compared to bath water therapy which needs 100 liters of water and 50 ml of 8-MOP. The cost of the drug is less and it is easy and less time-consuming with no systemic side effects when compared to topical psoralen therapy.

This treatment can be carried out at home with sunlight as the UVA source.

Disadvantage of bath-suit delivery are that the entire body surface especially face does not come in contact with the drug and the concentration of the drug may not be uniform in the bath suit.

PUVA turban therapy

This therapy has been used in the treatment of alopecia areata.

Methodology: A cotton towel is soaked with a 0.0001% 8-MOP solution (1 mg/L) at 37 degrees C, wrung gently to remove excess water and wrapped around the patient's head in a turban fashion for 20 min. This is directly followed by UVA radiation. Treatment sessions are three to four times per week. This therapy has been shown to be a well-tolerated and is an efficient therapeutic alternative in the treatment of alopecia areata.  

Oral treatment

In oral PUVA, 8-MOP is administered orally (0.6 to 0.8 mg per kilogram body weight) 1 to 3 h before exposure, depending on the absorption characteristics of the particular drug brand. The usual dosage for 5-MOP is 1.2 to 1.8 mg per kilogram body weight.

The initial UVA doses are established by either skin typing  or by MPD testing.  Doses are 4, 4.5 or 5 for skin over body and 5 or 6 J/cm ² for palms and soles. The MPD is defined as the minimal dose of UVA that produces a barely perceptible, but well-defined, erythema when template areas of the skin are exposed to increasing doses of UVA ranging from 0.5 to 5 J/cm ² . Erythema readings are performed 72 h after testing, at which time the psoralen phototoxicity reaction usually reaches its peak. The MPD test should be performed on previously nonexposed skin (e.g. buttocks). It is difficult to determine MPD in the Indian skin and therapy is started with a starting dose of 0.5 J/cm ² and increments can be made every second or third sitting.

Repeated exposures are required to clear PUVA responsive diseases and the frequency of treatments is reduced after satisfactory clearing of disease and the last UVA dose is used as a maintenance dose if maintenance treatment is planned. The duration of this maintenance phase and the frequency of treatments depend on the particular disease being treated and its propensity to relapse.

Eye protection with UVA-blocking glasses (B2 Toric glasses) is required from time of exposure to psoralen until sunset that day A sunscreen with an SPF of at least 15 is required for protection from a psoralen phototoxic reaction. Men should also shield their genitalia.

Diseases Treatable by PUVA Therapy

Alopecia areata
Atopic dermatitis
Cutaneous T-cell lymphoma
Dyshidrotic eczema
Graft versus host disease
Lichen planus
Palmophantar pustulosis
Parapsoriasis
Pityriasis lichenoides
Polymerphous light eruption
Pityriasis rubra pilaris
Psoriasis
Urticaria pigmentosa
Vitiligo

Side effects and contraindications
Because PUVA therapy is based on photosensitizing effects, it is contraindicated in patients with photosensitive diseases such as systemic lupus erythematosus and porphyria cutanea tarda. PUVA therapy is also contraindicated in pregnant women PUVA, because of concerns about possible teratogenicity therapy has both acute and chronic side effects. Acute effects include sunburn reactions, nausea, pruritus, headache and dizziness.

The most common chronic side effects of PUVA therapy include premature photoaging, pigmented macules, actinic keratoses, squamous cell carcinoma, basal cell carcinoma and, possibly, anterior cortical cataracts.

UVB

Types of UVB

Two types of UVB phototherapy are available: narrowband and broadband and the principles underlying these treatments and protocols used are different.

Therapeutic spectrum

A potential advance in UVB-based phototherapy has been the introduction of fluorescent bulbs (Phillips model TL-01) that deliver UVB in the range of 310 to 315 nm, with a peak at 312 nm. It has a relatively narrow spectrum of emission and results in a reduction in erythemogenic wavelengths in the 290-305 nm range and 5-6 fold increased emission of the longer UVB wavelengths, thereby resulting in a higher phototherapy index for psoriasis.

Mechanism of action

In psoriatics, NB-UVB phototherapy lowers peripheral natural killer cell activity, lymphocyte proliferation and immune regulatory cytokine production, by both Th1 (IL-2, IFN-g) and Th2 (IL-10) T-cell populations. In vitiligo, it results in stabilization of the depigmenting process the stimulation of residual follicular melanocytes.  

Dosing schedulePrior to phototherapy, the patients minimal erythema dose (MED) must be determined in order to establish the optimal dosage schedule. MED is determined by standard method.  A template with 20 apertures (10 on each side) of 1½ × 1½ cm ² is made over the back of a cotton suit used by operation theatre staff. Cotton flaps made over the apertures enables to either shut or keep the apertures open by using Velcro The source of NB - UVB is whole body phototherapy unit with 24 Philips TL-01 bulbs. To determine MED a single panel in the whole body unit with 6 bulbs is used. BB-UVB phototherapy panel with 8 bulbs is used to determine MED to BB. The irradiance from the source is determined using photometer. All the apertures are kept open and back-irradiated with 5 mJ of BB-UVB. One aperture is closed and remaining apertures are closed one after the other after delivering 5 mJ more than the previous aperture. Same procedure was repeated on the other half of the back starting with 50 mJ of NB - UVB and increasing the dose by 50 mJ for each aperture. The dosage schedule for BB - UVB (in mJ) was 5, 10, 15, 20, 225, 30, 35, 40, 45, 50 and for NB - UVB (in mJ) was 50, 100, 150, 200,250, 300, 350, 400, 450, 500. The readings were taken 24 h after exposure. For 311-nm therapy, the initial dose should be 70% MED in the interest of safety. The authors recommend that MED should be determined before NB-UVB therapy for all condition except vitiligo. Patients are treated three to five times per week. Although more sittings will be beneficial, two or three sittings are more cost effective and hence more acceptable. If the initial dose is tolerated, a 20 percent incremental increase of the previous dose is used at each visit. When a previous treatment results in erythema no treatment is given in the next schedule. Increments every second or third sitting is also effective (personal observation) possibly because sub erythemogenic dose of UVB is also as effective as erythemogenic dose. Another approach, as commonly practiced in India, involves a standard starting dose (280 mJ/cm ² ), with stepwise increase (usually 20%) depending upon the patient's erythema response. Since many patients have high MED, the first few sittings will be useless for which the patient will pay and in addition the time for response will increase.

In the photodermatoses, the approach is more cautious with only 10% incremental regimen on sun-exposed sites.  In case of mild erythema, the irradiation dose is held constant for subsequent treatments or until resolution of symptoms. The goal of therapy is to achieve persistent asymptomatic erythema. In case of painful erythema with or without edema/blistering, further treatment is withheld till the symptoms subside. After resolution of overdose symptoms, the dose administered is 50% of the last dose and subsequent increments should be by 10%. We would like to add a note that the percentages of increments are only recommendation and the physician should be guided by his own experience, patient's comfort and increments can be tailored on case to case basis.

UVB burn is unpleasant and if it occurs during initial phototherapy session the patient is always apprehensive about re-starting therapy. If the MED is detected at 475 mJ, 450 mJ can be considered as MED especially in Indian skin as erythema may not be detectable. If the patient is sedentary female or has sensitive skin or has atopic diathesis then initial treatment can be 50% of MED instead of 75%.

Indications

Vitiligo
Psoriasis
Atopic dermatitis
Other dermatoses

Prophylactic low dose NB-UVB has been found to be useful in various predominantly UVA induced photosensitivity disorders like polymorphic light eruption, actinic prurigo, hydroa vacciniforme and the cutaneous porphyrias by providing a hardening photoprotective effect.

Long term use and adverse effects

In addition to the expected immediate sunburn effects, chronic NB-UVB exposure is likely to increase photoageing and the risk of carcinogenesis. However, according to a dose response model it has been calculated that the long-term risk for carcinogenesis with its use may be less than that of PUVA therapy.  Clinical experience with NB-UVB is limited and currently there is no established safe limit for its maximum safe duration of use in vitiligo. In children, the maximum duration allowed is 12 months.

Broadband UVB phototherapy

High-dose UVB phototherapy using sunlamp bulbs (broadband UVB) was an effective treatment in many patients with psoriasis. High dose means using a treatment schedule aimed at staying close to or above the erythema threshold of the patient throughout the course of treatment.

NB UVB is more effective than BB UVB. Both can cause sun burn but BB is more likely to burn than NB UVB. The advantage of BB is very short duration of exposure and rapid clearance especially in psoriasis. BB is reported to be carcinogenic especially among whites. This may not be true for our skin. No case of BB induced malignancy is reported from India. However since lamps are only manufactured in Western countries and since they have abandoned the use of BB UVB and have stopped manufacturing the tubes we have no choice but to stop using the light which is cheaper unless we manufacture the bulb in India.

Combination Therapy

Phototherapy may be combined with topical or systemic agents to achieve higher clearance rates, longer disease free intervals and a lower carcinogenic risk.  Topical agents. Include anthralin, vitamin D analogues, retinoids, glucocorticoids, emollients, saltwater baths and tar. The combination of either broadband UVB or 311 nm UVB therapy with calcipotriol increases the therapeutic efficacy of phototherapy and reduces the irritation caused by calcipotriol. 

Another combination phototherapy of psoriasis is narrowband UVB irradiation and topical tazarotene gel. The addition of tazarotene broadband or narrowband UVB phototherapy was found to promote more effective, faster clearing of psoriasis when compared to either type of phototherapy alone.

Pretreatment with tazarotene gel three times per week for two weeks before phototherapy significantly reduces the mean minimal erythema dose for UVB and the mean UVA exposure required to induce immediate pigment-darkening. Thus, UVB and PUVA therapy can be initiated at lower doses than usual when used in combination with tazarotene.  

Topical application of emollients alters the optical properties of psoriatic lesions, improve transmission of UVB and leads to increased efficacy.  The systemic use of glucocorticoids in combination with photo (chemo) therapy is limited to special indications, such as generalized pustular psoriasis. Also, combination regimens of UVB therapy with methotrexate or cyclosporine A are not advisable, because both substances increase the possibility of UV-induced skin tumors. Retinoids are the most widely used agents for systemic treatment in combination with phototherapy)

The advantage of combining retinoids and UVB irradiation is two-fold: (1) retinoids exert antipsoriatic effects, which might act synergistically with UVB phototherapy; and (2) they have anticarcinogenic effects and thereby could lower the increased skin cancer risk resulting from long-term UVB therapy. Combination regimens with broadband UVB or oral retinoid therapy together induced improvement in psoriatic patients more quickly than with phototherapy alone and reduced the number of treatments and cumulative UV doses.  Similar results were obtained when acitretin, the major metabolite of etretinate, was used in combination with broadband UVB or 311-nm UVB therapy.

Combinations of psoralen, UVA and UVB

Combinations of PUVA and UVB have shown increased efficacy in the treatment of psoriasis. For recalcitrant disease, a combination of PUVA and UVB clears psoriasis more rapidly than PUVA or UVB, buttressing the concept that UVB and PUVA have different and perhaps complementary mechanisms. Similarly, 311-nm exposure enhances the phototoxic activity of bath-PUVA. Bath-PUVA with nbUVB clears psoriasis with fewer exposures and lower cumulative UVA doses under the same minimally erythemogenic conditions.  

Psoralen has not been shown to add to the efficacy of narrow-band UVB in the treatment of vitiligo. 

Although PUVB and nbPUVB are efficacious in the treatment of skin disease, neither has established a utility over nbUVB or PUVA alone. The long-term safety of PUVB or nbPUVB remains to be defined. Further evaluations of psoralen and UVB need to be conducted.

UVA-1 phototherapy

Conventional UVA1 treatment emits wavelengths mainly between 340 and 400 nm, but may also produce scattered radiation >530 nm including infrared irradiation (780-3000 nm). It may be accompanied by extensive heat load predominantly generated by infrared irradiation (780-3000 nm) and/or insufficient cooling systems of the phototherapy devices. UVA-1 phototherapy is quite expensive and requires a special light source not readily available everywhere. It is used for the treatment of scleroderma, chronic GvHD, extragenital LSA or sclerodermoid rarities and other disorders affecting the connective tissue.  It is also effective in the treatment of inflammatory skin diseases such as acutely exacerbated atopic dermatitis, urticaria pigmentosa and disseminated granuloma annulare. 

Excimer lasers

Excimer 308-nm laser is a laser light source that delivers a specific wavelength (308 nm) of UVB radiation. This is beneficial in the treatment of psoriasis. The UV ray generated by the excimer laser focuses on the psoriatic lesion. The advantages are that healthy skin surrounding the areas of psoriasis is not exposed to radiation; higher dose of radiation can be used to induce a visible reaction in the psoriatic plaque Most clinical studies on the use of excimer laser therapy have focused on patients with localized psoriasis involving less than 10 or 20% of the body. It is used to treat a select group of patients with localized, refractory plaque psoriasis (e.g. patients with thick, scaled plaques on the knees and elbows, which are resistant to any conventional treatment).  Side effects include erythema, blisters, hyperpigmentation and erosions. Although the risk from excimer laser therapy is unknown, research to date suggests it is less risky than narrowband UVB as it does not expose the whole body to UV radiation.

Photo dynamic Therapy

Photodynamic therapy (PDT) aims to destroy the desired target selectively, thereby avoiding or minimizing damage to vital structures. The photodynamic reaction consists of the excitation of photosensitizers (mainly porphyrins) by visible light in the presence of oxygen, resulting in the generation of reactive oxygen species, particularly singlet oxygen. These reactive oxygen species mediate cellular and vascular effects depending on the tissue localization of the photosensitizer. This results in a direct or indirect cytotoxic effect on the target cell.  In dermatology, PDT has been used effectively for precancerous and malignant conditions such as actinic keratosis, basal cell carcinoma, Bowen's disease and superficial squamous cell carcinoma, as well as for inflammatory dermatoses such as psoriasis or localized scleroderma.

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