Reduced Sunlight Exposure Research Articles

Influence of weather on seizure frequency — Clinical experience in the emergency room of a tertiary hospital

IntroductionSome patients with epilepsy identify weather as a typical seizure trigger. However, it is yet to be confirmed. Thus, we aimed to evaluate possible relationships between daily meteorological conditions and the daily incidence of seizures. MethodsThis was a retrospective single center study that included adult patients who were admitted to the emergency room of a tertiary hospital in Lisbon, with a seizure, between January and December 2015. The influence of temperature, atmospheric pressure, relative humidity, wind, precipitation, sunlight duration, and the seasons on seizure frequency was evaluated. ResultsThree hundred seven seizure episodes were included (from 286 patients) in a total of 365 days, 117 (38.1%) first unprovoked seizures and 190 (61.9%) with previous seizure episodes. There were 82 days with higher incidence of seizures (≥2) and 171 days without seizures. We found a statistical significant relation between lower ambient temperatures, higher atmospheric pressure, and higher maximum humidity with days with two or more seizures. We also found a statistically significant higher incidence of seizures in the winter days (p-value: 0.001) and in days with lower daylight duration (10.8 vs. 12.7 h; p-value: 0.0001). With the exception of humidity, these findings remained true when analyzing the subgroup of patients with previous seizures, but there was no significant difference in the subgroup of first unprovoked seizures. ConclusionsOur results support the possible influence of the weather on seizure frequency in the overall admissions of the emergency department of a tertiary hospital. In particular, these findings suggest that winter conditions, such as, lower ambient temperatures, higher atmospheric pressure, higher humidity, and reduced sunlight exposure, may have impact in the occurrence of higher incidence of seizures in patients with epilepsy.

High Vitamin D-Binding Protein Concentration, Low Albumin, and Mode of Remission Predict Relapse in Crohn's Disease.

Vitamin D (25(OH)D) deficiency occurs in active Crohn's disease (CD) and may be secondary to reduced sunlight exposure and oral intake. Vitamin D-binding protein (VDBP) levels, however, fluctuate less with season and sunlight. The aim, therefore, was to examine patients with CD in remission and determine any associations between VDBP, serum 25(OH)D, and the calculated free 25(OH)D concentrations with the risk of disease flare. Subjects were identified from prospectively maintained inflammatory bowel disease databases at 3 teaching hospitals in Australia. Patients were in steroid-free clinical remission at the time of blood draw and were followed for at least 12 months. Total and epimer-25(OH)D3, VDBP concentrations, and genotypes were determined. A total of 309 patients with CD (46% men) met the inclusion criteria. A disease flare occurred in 100 (32.4%). Serum 25(OH)D3 was deficient (<50 nmol/L) in 36 (12%) and insufficient (50-75 nmol/L) in 107 (35%) patients. Total, free, and epimer-25(OH)D3 serum levels did not predict disease flare. Higher VDBP concentrations, however, significantly correlated with increased risk of disease flare (hazard ratio 1.2, 95% CI, 1.0-1.5). On multivariate analysis, VDBP concentration, low albumin, and medication-induced remission were significantly more associated with disease flare. VDBP genotypes were significantly associated with 25(OH)D and VDBP concentrations but not disease flare. Vitamin D deficiency was uncommon in our patients with CD in remission, and serum 25(OH)D3 did not predict disease flare, whereas higher VDBP concentrations were significantly associated with disease flare. Further investigations to explore the possible mechanisms for this association are warranted.

ASCIA‐P55: THE INFLUENCE OF VITAMIN D AND UV‐LIGHT EXPOSURE ON THE DEVELOPING IMMUNE PHENOTYPE IN INFANCY

Low levels of vitamin D have been linked to allergies in children, the potential result of lifestyle and reduced sunlight exposure. Vitamin D supplementation is already in use in many countries. This has not occurred in Australia, largely due to the belief that children are exposed to adequate sunlight. However, there is growing evidence of suboptimal vitamin D levels and a pressing need to understand if this is a contributing factor to the dramatic increase in infant allergy. In this double-blind, placebo-controlled randomised trial, high risk infants are orally supplemented with either 400 IU vitamin D/day or placebo from birth to 6 months of age. Uniquely a UV-dosimeter is also worn. Blood samples are collected at birth, 3, 6 and 12 months of age to determine relationships between oral vitamin D supplementation and UV-light exposure with blood 25(OH)D concentration, immune cell function responses to allergens and on the development of allergic conditions in early childhood. To date initial findings (n = 42) have found that vitamin D and UV exposure, both play a role in maintaining a suppressive Treg pool characterized by a greater expression of HLA-DR and CD45RA, and fewer CD69 + cells. Additionally a lower percentage of circulating mature dendritic cells (DC) was found. Beyond this we have found correlations between average daily UV exposure in the first 3 months and DC with reduced propensity for T cell activation at 6 months. Early preliminary results from this study demonstrate novel findings that vitamin D levels and UV exposure in infancy have important consequences for the developing immune phenotype in a population at hereditary risk of allergic disease. The findings offer insight into possible immunological mechanisms behind the reported inverse associations between vitamin D status and allergic disease.

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

BackgroundVitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake.MethodsWe searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup’ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value.ResultsWe identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes.ConclusionWe provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0538-y) contains supplementary material, which is available to authorized users.

The impact of vitamin D deficiency on patients undergoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes.

Vitamin D deficiency is common among kidney transplant (KT) recipients because of reduced sunlight exposure, low intake of vitamin D, the immunosuppressive drug regimen administered, and steroid therapy. Glucocorticoids regulate expression of genes coding for enzymes that catabolize vitamin D, further reducing its level in serum. Although vitamin D primarily regulates calcium homeostasis, vitamin D deficiency is associated with the risk of several diseases, such as diabetes mellitus and tuberculosis. Aim of this review is to highlight endocrine and metabolic alterations due to the vitamin D deficiency by evaluating the mechanisms involved in the development of KT-related disease (cardiovascular, bone mineral density, and new-onset diabetes after transplantation). Next, we review evidence to support a link between low vitamin D status and KT-related diseases. Finally, we briefly highlight strategies for restoring vitamin D status in KT patients.

Vitamin D and Hypertension: An Overview of Current Scenario

India has become the capital of all communicable diseases and noncommunicable diseases like hypertension and diabetes. Vitamin D deficiency is also very high in the Indian subcontinent (as high as 80–90%). Therefore, it is possible that these issues are interrelated, or we should look for possible relations. The landmark study by us suggested the cause of vitamin D deficiency as poor dietary intake or in other words due to malnu trition. Vitamin D deficiency is multifactorial in etiology; the etiological factors vary from place to place and person to person. The three primary reasons for the deficiency are: lack of balanced diet, reduced sunlight exposure and increased melanin in the skin. Even if, by chance, someone gets adequate vitamin D from diet and sunlight, its activation in the liver and kidneys is defective due to increasing prevalence of liver and kidney diseases. Liver diseases are on the increase due to overeating with consequent obesity and nonalcoholic liver disease, or due to alcohol intake and exposure to hepatotoxic agents or infections. Subclinical liver disease is now widely prevalent in the people with consequent poor activation of vitamin D. Increasing renal diseases due to several reasons and the lack of vegetables and fruits consumption with consequent hypomagnesemia contribute to poor 1-hydroxylation in the kidneys. Lack of intake of balanced diet, lack of outdoor exercises and eating more food are all lifestyle issues, and the same are the causes for diseases, like hypertension, diabetes, ischemic heart disease (IHD), strokes and cancers and, therefore, the link between vitamin D deficiency and these diseases become very obvious. It is only natural that we see vitamin D deficiency in all the diseases, or supplementation of vitamin D benefits all the patients. To tackle the problem of vitamin D deficiency in India, we need to address all the healthcare issues simultaneously and empower the people for regular intake of balanced diet, doing regular exercise and exposure to sunlight through systematic and meticulous social, educational, agricultural and financial reforms. Therefore, all disease control programs in India should focus on empowering the people, by the necessary social reforms and its implementation. As an interim measure, fortification of foodstuffs like oil or wheat-flour also may be tried till such time that all sections of the society are empowered for taking balanced diet regularly.

Vitamin D status in Irish children and adolescents: value of fortification and supplementation.

Vitamin D has important skeletal and extraskeletal roles but those living at northerly latitudes are at risk of suboptimal levels because of reduced sunlight exposure. To describe the vitamin D status of Irish children and identify factors predictive of vitamin D status. A prospective cross sectional study was undertaken over a 12 month period. Two hundred and fifty two healthy children attending for minor medical or surgical procedures were recruited. All had 25-hydroxyvitamin D (25OHD), parathyroid hormone and bone profiles measured. The mean (standard deviation) for 25OHD was 51(25) nmol/L (20.4 (10) ng/mL). Forty-five percent had levels >50 nmol/L (20 ng/mL). The following variables were significantly associated with 25OHD levels >50 nmol/L (20 ng/mL): sample drawn in April-September, use of vitamin D supplements, consumption of formula milk, and non-African ethnicity. More than half of the children in this study had 25OHD levels less than 50 nmol/L (20 ng/mL). Vitamin D status was significantly improved by augmented oral vitamin D intake.

Prevalence of Vitamin D Deficiency in Patients With Hip Fracture Seen in an Orthogeriatric Service in Sunny Singapore

Vitamin D deficiency is common in older adults in Western countries with seasonal winters, when the amount of sunlight is much reduced. There is a paucity of data on the prevalence of vitamin D deficiency in patients with hip fracture in countries such as Singapore where the climate is predominantly tropical. In this study, our aims were to ascertain the prevalence of vitamin D deficiency and risk factors associated with vitamin D deficiency in hospitalized elderly patients with hip fracture in Singapore. We prospectively studied 485 patients with hip fracture admitted to the orthopedic department over a 1-year period. Nonfragility fractures and younger patients (patients <60 years and those with high-impact injuries) were excluded. Data on patient demographics, comorbidities, functional status, and serum 25-hydroxyvitamin D3 levels were collected. Vitamin D deficiency was defined using Holick classification. Vitamin D levels were available for 412 patients. Vitamin D deficiency was present in 57.5% (n = 237). Prevalence of vitamin D insufficiency was 34.5%, with only 8% of patients having normal vitamin D levels. Univariate analyses showed Malay race and functional factors (being housebound, requiring bathing and dressing assistance) to be associated with vitamin D deficiency. However, only ethnicity and housebound patients were significant in the multivariate model. Vitamin D deficiency and insufficiency are common in patients with hip fracture in Singapore. Vitamin D deficiency was associated with being housebound and those of Malay ethnicity. Clothing habits resulting in reduced sunlight exposure may increase the risk of vitamin D deficiency.

Vitamin D and prevention of diabetes: is lifelong endogenous vitamin D needed?

Vitamin D deficiency is a risk factor for skeletal diseases, but whether it contributes to non-skeletal diseases such as cancer, cardiovascular diseases, and diabetes is unclear.1–3 A disparity clearly exists between observational studies showing vitamin D deficiency as a risk factor for various non-skeletal diseases, and randomised controlled trials that have largely failed to prove that vitamin D supplementation has significant benefits.1–3 A simple explanation for these results is that vitamin D deficiency is merely a marker of illness and is low because of, for example, reduced sunlight exposure, inflammation affecting vitamin D metabolism, or obesity with vitamin D trapped in adipose tissue.

A comparison of hip fracture incidence rates among elderly in Sweden by latitude and sunlight exposure

Research has shown that hip fracture risk increases with latitude; hypothetically due to reduced sunlight exposure and its effect on bone quality. Sweden, with large differences in latitude and UV radiation, is ideal to study in order to analyse the association between latitude and UV radiation on age- and sex-specific hip fracture rates among elderly. Aggregated (2006-2008) age- and sex-specific hip fracture data was obtained for each Swedish municipality as well as the municipality's latitudinal coordinates and aggregated (2006-2008) UV radiation levels. Pearson correlations were calculated between hip fracture incidence rates, latitude and UV radiation. Independent t tests were calculated on tertile-categorized latitudinal data in order to investigate the difference in hip fracture risk between these categories. Statistically significant correlations were seen in all groups between hip fracture incidence rates and latitude as well as UV radiation. The independent t tests showed that this correlation was mainly due to high incidence rates in high latitude municipalities. Statistically significant correlations are seen between hip fracture incidence rates and latitude as well as UV radiation in Sweden and the northern parts of Sweden have an increased risk of hip fractures compared to the middle and southern parts. To our knowledge this is the first study using a national discharge register that shows this relationship and provides a starting point for further research to investigate why populations in northern Sweden have a higher risk of hip fractures compared to other Swedish regions.

Abstract 2591: Relationship Between Sunlight and Temperature Exposure to Stroke Incidence in the Reasons for Geographic and Racial Differences in Stroke (regards) Study

INTRODUCTION: Stroke incidence is higher during the winter, indicating that long and short-term sunlight exposure may contribute to stroke incidence. HYPOTHESIS: Reduced sunlight exposure and extreme temperatures are associated with increased stroke incidence. METHODS: Data were obtained from the REGARDS study, a national population-based cohort of 30,239 enrolled from 2003-2007 consisting of black and white participants, aged 45+. A centralized phone interview was used for medical history, in-home evaluation for physical measures, and a self-administered questionnaire for complete residential histories (city/state) from birth. The risk of stroke and sunlight exposure was studied in the 16,529 participants that were free of stroke and coronary artery disease at baseline and had lifetime residential histories available. Fifteen-year residential history merged with satellite and ground monitor data were used to determine sunlight and temperature exposure. Since long-term sunlight and temperature measures have not been extensively used in health studies, we performed exploratory analyses to determine which measures carried the strongest relationships with stroke. Fifteen, ten, five, two and one-year exposures were used to predict stroke incidence using Cox proportional hazard models. Potential demographic, behavioral, and medical confounders and mediators were included during model-building. RESULTS: Over an average follow-up period of 5.0 years, 351 had an incident stroke. Monthly average sunlight and maximum temperature exposures at residence exhibited the strongest relationships with stroke. It was determined that the shortest period of sunlight exposure, one year, exhibited the strongest relationship. After adjustment for other covariates, the previous year’s monthly average sunlight exposure below the median predicted increased risk of stroke (HR=1.61 (95% CI: 1.15, 2.26)). Temperature exhibited a J-shaped relationship with stroke incidence. CONCLUSION: This is the first report showing a relationship between sunlight and stroke. In addition, we confirmed earlier studies that both hot and cold temperatures are related to increased stroke incidence. The biological pathway of this relationship is not clear. Future research will show whether this finding stands, the pathway for this relationship, and if it is due to short or long-term exposures.

The role of light in the regulation of ascorbate metabolism during berry development in the cultivated grapevineVitis viniferaL.

The accumulation of L-ascorbate (Asc) in fruits is influenced by environmental factors including light quantity. Fruit exposure to ambient light is often reduced by the surrounding leaf canopy, and can be altered by cultivation practices. The influence of reduced sunlight exposure on the accumulation of Asc and its catabolites was investigated in field-grown berries of the cultivated grapevine Vitis vinifera L. cv. Shiraz. Growth under sunlight-eliminated conditions resulted in reduced berry fresh weight, chlorosis and a reduced total L-ascorbate pool size. The concentration of the Asc catabolite L-tartaric acid (TA) was reduced in berries grown without light. Conversely, concentrations of oxalic acid (OA), an alternative catabolite of Asc, and malic acid (MA), were unaffected by shading the berries during development. Brief and significant reductions in transcription of the Asc metabolic genes were observed in shade-grown berries after 4 weeks of dark acclimatisation whilst a key TA biosynthetic gene was not regulated by light. The results demonstrate that light-regulation of Asc and TA occurs only at brief stages of development and that OA and MA accumulation is light independent. Additionally, the comparable ratios of TA product to Asc precursor under both light regimes suggest that the diversion of Asc to TA is driven by factors that are not responsive to light. These findings suggest that an altered light regime is not the key to manipulating TA or MA levels in the harvested berry.

Searching for pale, getting rickets

Case reportSaid BamashmusA 36-year-old woman presented with her 2-year child inthe out-patient orthopaedic department of our hospital. Shecomplained that her little boy was unable to walk properlywithout support. The child looked intelligent, aware ofwhat was happening around him. However he was hypo-tonic with muscular weakness, cranial sutures were stillwidened and dental eruption was delayed. No otherabnormal findings were found at the physical examination.Urine and essential blood tests were normal except for anincrease in the serum alkaline phosphatase (1,253 IU/ml).The X-ray performed to his legs showed radiologic alter-ation at the epiphyseal growth plate due to decreased cal-cification of the hypertrophic zone and inadequatemineralization of the primary spongiosa. The orthopaedistasked to visit also the 15-year-old sister who was accom-panying the little infant. The young woman had skeletalpain and most significantly a ‘‘rachitic rosary’’ due theprominence of the costochondral junctions.These findings confirmed the suspect of the orthopaedistand he diagnosed in both patients the presents of rickets.While speaking with the mother he found out that shewanted her children to be as much white as possible anddid not let them get in contact with sunlight and obliged herdaughter to dress the dark nighab since an early age. Thephysician advised the mother to give her children food richwith calcium and oral vitamin D, but explained and con-vinced her that sunlight is more important for the goodhealth of her children than any other treatment. At the6 months follow up, the little boy was fine and able to walkcorrectly and the clinical findings for his sister wereimproving.CommentMohamed Bamosmoosh, Pietro Amedeo ModestiA porcelain complexion has been coveted through the ages,but pale skin also comes with a host of challenges. Thesigns of rickets at physical examination are now rare inWestern countries where the importance of the diet rich incalcium and vitamin D as well as of sunlight for a correctgrowth of infants and adolescents is well recognized. A lowintroduction of vitamin D and calcium is indeed mainlyrelated to the socio-economic situation in developingcountries (Nigeria, Ethiopia) [1–3]. A dark skin howeverrequires a longer time exposure to the sun ultraviolet (UV)rays than a pale one and this is especially important forimmigrants to countries characterized by few sunlighthours [4]. More recent reports are now indicating that alsoin countries, such as India, Pakistan, Iran and the ArabianPeninsula [5–7] rickets in adolescents, especially female,may be also associated to a reduced sunlight exposure ofthe children. In particular, in addition to indoor confine-ment for climatic conditions, two other two social habits

A Case of Osteomalacia with Multiple Fractures and Hypocalcemia Associated with Phenytoin Therapy

Many studies have shown that patients taking antiepileptic drugs are at an increased risk for metabolic bone disease and low bone mineral density. Traditionally, this has been attributed to alterations in vitamin D metabolism by antiepileptic drugs which induce hepatic microsomal cytochrome P450 enzyme. However, there appear to be multiple mechanisms for antiepileptic drug-induced bone loss including lack of physical activity, reduced sunlight exposure, increased propensity for falling, and fractures associated with seizures or loss of consciousness. We experienced a case of antiepileptic drug-induced osteomalacia in a 63-year-old woman who had been on phenytoin for 8 years and was admitted with hypocalcemic seizures and multiple pathological fractures. This patient also had other risk factors for osteomalacia including reduced sunlight exposure, prolonged immobilization, and decreased dietary vitamin D intake. We discontinued phenytoin, and started calcium and vitamin D replacemen t. The patient's serum calcium and vitamin D level were normalized after treatment. Metabolic bone disease including osteomalacia should be considered in patients who are taking antiepileptic drugs especially those who are exposed to other risk factors. (J Korean Endocr Soc 24:212~216, 2009) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Genetic Aspects of Porphyria Cutanea Tarda

Porphyria cutanea tarda (PCT) is caused by disruption of heme biosynthesis at the step catalyzed by uroporphyrinogen decarboxylase. The patients present with photosensitive cutaneous lesions, hepatic pathology (including elevated porphyrin levels), and increased excretion of porphyrins. Therapy consists of removing the exacerbating factors of PCT (reduced sunlight exposure, abstinence from alcohol use, decreased estrogen exposure, and treatment for viral infections), decreasing body iron stores (by therapeutic phlebotomy or by the use of the new orally active iron chelators), and, in some instances, the use of low-dose antimalarials. Recent advances in genetics and genomics have allowed DNA testing for porphyria cutanea tarda and are likely to be instrumental in developing improved, gene-based treatments and in finding genetic loci (in addition to uroporphyrinogen decarboxylase) involved in the clinical expression of this disease.

Vitamin D status in patients affected by Smith‐Lemli‐Opitz syndrome

Smith-Lemli-Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis characterized by developmental delay and multiple malformations. Some of the patients have skin photosensitivity and therefore tend to avoid direct exposure to sunlight.SLOS patients typically have low concentrations of cholesterol and abnormally high concentrations of its precursor 7-dehydrocholesterol (7-DHC) in biological fluids and tissues. 7-DHC is also a precursor in the cutaneous synthesis of vitamin D. Sunlight exposure plays a major role in this pathway and reactions transforming 7-DHC into vitamin D and then into 25-hydroxyvitamin D are known not to be specifically regulated. The aim of this study was to evaluate vitamin D status in SLOS patients. We measured 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations and markers of calcium metabolism in five SLOS patients. Despite abnormally high concentrations of 7-DHC, circulating concentrations of vitamin D metabolites were not significantly different from appropriate controls matched for sex, age and season of blood collection. The analysis of historical serum samples stored in our laboratory from the same cases plus 10 other SLOS patients further supported these findings. Our data suggest that SLOS patients have a peculiar vitamin D metabolism that protects them from vitamin D intoxication. This appears to be due in most cases to decreased transformation of 7-DHC into 25-hydroxyvitamin D, perhaps depending on reduced sunlight exposure as a consequence of photosensitivity. Possible alternative mechanisms are discussed.

Pathophysiology of bone loss in patients receiving anticonvulsant therapy

Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Although early reports of bone disease in patients with epilepsy often involved institutionalized patients, who may be at risk because of lack of physical activity, reduced sunlight exposure, and poor nutrition, low bone density has also been reported in well-nourished, ambulatory outpatients with epilepsy. Traditionally, attention to the problem of AED-induced bone loss has been focused on those drugs that induce the hepatic cytochrome P450 enzyme system, thereby increasing the metabolism of vitamin D. However, the mechanisms of AED-induced bone loss appear to be multiple, and all types of AEDs are potentially implicated. Besides hepatic enzyme induction, mechanisms may include direct effects of AEDs on bone cells, resistance to parathyroid hormone, inhibition of calcitonin secretion, and impaired calcium absorption. An understanding of bone biology and the pathophysiology of bone loss can aid in the identification and monitoring of patients at risk and in the planning of appropriate prophylactic and therapeutic measures, by which most of the morbidity associated with AED-induced bone loss can be prevented.

Chronic prostatitis.

This review covers recent developments in the classification, epidemiology, aetiology, diagnosis and treatment of patients diagnosed with chronic prostatitis (NIH classification types II, IIIa/IIIb and IV prostatitis) in the period of review (2001-2002). Recent studies highlight some of the problems with the 1995 NIH classification. Epidemiological studies have confirmed that "prostatitis" is common, with a prevalence of 10-15%. Associations of prostatitis include benign prostatic hyperplasia, sexually transmitted disease, lower urinary tract symptoms, stress, and reduced sunlight exposure. Elevated levels of cytokines in the seminal plasma and prostatic secretions have been detected in men with chronic prostatitis compared with normal individuals, suggesting an active inflammatory process in the male genital tract. This inflammatory reaction may be mediated by an adaptive immune response directed against a genital tract antigen(s) (autoimmunity). Increased levels of bacterial 16S ribosomal DNA in the prostates of men with chronic prostatitis compared with controls are compatible with the notion that a bacterial inflammatory event initiates an auto-immune process; however, the role of bacteria in the continuation of symptoms is unknown. The aetiology of chronic pelvic pain syndrome is still not certain, although an auto-immune process is favoured. Further research is required to determine the putative auto-antigen, the immune responses of patients, the role of bacteria in the inflammatory process, and the patients' pain response to genitourinary insults. As yet no diagnostic tests (other than to eliminate other pathology) and few treatments for chronic prostatitis can be recommended on the basis of scientific evidence.

Sunlight, cholesterol and coronary heart disease.

We investigated the relationship between geography and incidence of coronary heart disease, looking at deficiency of sunlight and thus of vitamin D as a factor that might influence susceptibility and thus disease incidence. Sunlight deficiency could increase blood cholesterol by allowing squalene metabolism to progress to cholesterol synthesis rather than to vitamin D synthesis as would occur with greater amounts of sunlight exposure, and the increased concentration of blood cholesterol during the winter months, confirmed in this study, may well be due to reduced sunlight exposure. We show evidence that outdoor activity (gardening) is associated with a lower concentration of blood cholesterol in the summer but not in the winter. We suggest that the geographical variation of coronary heart disease is not specific, but is seen in other diseases and sunlight influences susceptibility to a number of chronic diseases, of which coronary heart disease is one.

ROLE OF VITAMIN D, ITS METABOLITES, AND ANALOGS IN THE MANAGEMENT OF OSTEOPOROSIS

Vitamin D and its metabolites are well-established regulators of bone mineral homeostasis. Their clearest role is in the prevention and treatment of rickets and osteomalacia, bone diseases characterized by inadequate bone formation, and mineralization. Much of the effectiveness of vitamin D and its active metabolite 1,25(OH)2D in treating such disorders rests with their ability to increase serum levels of calcium and phosphate principally by stimulating intestinal calcium and phosphate absorption. Osteoporosis is not a disease resulting from obvious deficiencies in vitamin D, calcium, and phosphate. More subtle deficiencies, however, may be found, especially among the elderly with decreased intake of dairy products, reduced sunlight exposure, and less efficient intestinal absorption of bone minerals. Such subtle deficiencies may account for the ability of vitamin D and calcium supplementation to have a beneficial effect on bone mineral density in this population. Estrogen administration to postmenopausal females raises 1,25(OH)2D levels, presumably through increased renal production, and this increase is associated with increased intestinal calcium transport. Serum measurements of the vitamin D metabolites in general, however, and 1,25(OH)2D in particular do not consistently show evidence of a decrease at the time of menopause. Although most studies show a fall in intestinal calcium transport with age, which can be reversed with 1,25(OH)2D or estrogen, even these observations have not been found consistently. Thus, some investigators have addressed the issue of tissue resistance to 1,25(OH)2D and have noted decreased VDR in the intestine and reduced 1,25(OH)2D accumulation by bone with age. Despite no obvious deficiency of vitamin D in most patients with osteoporosis, clinical trials with vitamin D or 1,25(OH)2D show promise. Vitamin D treatment will probably prove most efficacious in populations with marginal vitamin D intake and/or limited sunlight exposure; high doses would not be required, and the treatment would be safe. This would be a physiologic and not a pharmacologic use of vitamin D. The use of 1,25(OH)2D for treatment of osteoporosis in individuals with adequate nutrition and sunlight exposure may require somewhat higher than physiologic doses to be effective. Perhaps such doses are necessary to stimulate osteoblast activity and/or differentiation; by raising the serum calcium level, such doses of 1,25(OH)2D might block its otherwise stimulatory effect on osteoclast number and activity. Such doses run the risk of hypercalcemia and hypercalciuria, leading to nephrolithiasis and/or nephrocalcinosis. These undesirable side effects appear to be less common with the use of 1 alpha OHD compared with 1,25(OH)2D, but this may be because of the lower levels of calcium consumption in Japan where 1 alpha OHD is widely prescribed.(ABSTRACT TRUNCATED AT 400 WORDS)