Ecological impact of pharmaceutical pollutants and options of river health improvements - A risk analysis-based approach.

Pharmaceuticals are one of the emerging pollutants (EPs) in river waters across the world. Due to their toxic effects on aquatic organisms, they have drawn the global attention of the scientific community concerned with river ecosystems. This paper reviews the existing occurrence data for various pharmaceutical pollutants (PPs) reported in river waters in some part of the world and their ecological impacts. Using algae, macroinvertebrates (MI), and fish as biotic indicator groups in water to reflect river health conditions, an attempt has been made to assess the ecological risk due to the presence of PPs in the water environment. After ascertaining the predicted no-effect concentration (PNEC) of PPs for selected groups of aquatic organisms, the risk quotient (RQ) is estimated based on their measured environmental concentration (MEC). When MEC > PNEC and RQ > 1 for any of the biotic indicator, ecologically it is 'high risk' condition. The determination of PNEC uses a minimum assessment factor (AF) of 10 due to uncertainty in data over the no observed effect level (NOEL) or lowest observed effect level (LOEL). Accordingly, MEC 10 times higher than PNEC, (RQ = 10) represents a threshold risk concentration (RCT) beyond which adverse effects may start showing observable manifestations. In the present study, a new classification system of 'high risk' conditions for RQ = 1-10 has been proposed, starting from 'moderately high' to 'severely high'. For RQ > 10, the ecological condition of the river is considered 'impaired'. For river health assessment, in the present study, the whole range of physico-chemical characteristics of river water quality has been divided into three groups based on their ease of measurement and frequency of monitoring. Dissolved oxygen related parameters (DORPs), nutrients (NTs), and EPs. PPs represent EPs in this study. A framework for calculating separate indicator group score (IGS) and the overall river health index (RHI) has been developed to predict indicator group condition (IGC) and river health condition (RHC), respectively. Color-coded hexagonal pictorial forms representing IGC and RHC provide a direct visible perception of the existing aquatic environment and a scientific basis for prioritization of corrective measures in terms of treatment technology selection for river health improvements. The analyses indicate that many rivers across the world are under 'high risk' conditions due to PPs having MEC > PNEC and RQ > 1. Up to RCT, (where RQ = 10), the 'high risk' condition varies from 'moderately high' to 'severely high'. In many instances, RQ is found much more higher than 10, indicating that the ecological condition of river may be considered as 'impaired'. Algae is the most frequently affected group of biotic indicators, followed by MI and fish. A review of treatment methods for selection of appropriate technology to reduce the pollution load, especially PPs from the wastewater streams has been summarized. It appears that constructed wetlands (CWs) are at present the most suitable nature-based solutions, particularly for the developing economies of the world, to reduce the concentrations of PPs within limits to minimize the ecological impacts of pharmaceutical compounds on biotic indicators and restore the river health condition. Some suggestive design guidelines for the CWs have also been presented to initiate the process.

Pharmaceuticals in water as emerging pollutants for river health: A critical review under Indian conditions.

The wastewaters from pharmaceutical manufacturing units, hospitals, and domestic sewage contaminated with excretal matters of medicine users are the prime sources of pharmaceutical pollutants (PPs) in natural water bodies. In the present study, PPs have been considered one of the emerging pollutants (EPs) and a cause of concern in river health assessment. Beyond the reported increase in antibiotic-resistant bacteria (ABRB), PPs have been found adversely affecting the biotic diversity in such water environments. Considering Algae, Macroinvertebrates, and Fishes as three distinct trophic level indicators, the present study puts forward a framework for showing River Health Condition (RHC) based on the calculation of a River Health Index (RHI). The RHI is calculated using six Indicator Group Scores (IGS) which individually reflect river health in a defined category of water quality characteristics. While Dissolved Oxygen Related Parameters (DORP), Nutrients (NT), and PPs are taken as causative agents affecting RHCs, scores of Algal-Bacterial (AB) symbiosis, Macroinvertebrates (MI), and Fishes (F) are considered as an effect of such environmental conditions. Current wastewater treatment technologies are also not very effective in the removal of PPs. The objective of the present study is to review the harmful effects of PPs on the aquatic environment, particularly on the chemical and biotic indicators of river health. Based on predicted no-effect concentrations (PNEC) for algae, macroinvertebrates, and fishes in the aquatic environment and measured environmental concentration (MEC) in the river, the estimated risk quotient (RQ) for norfloxacin in the Isakavagu-Nakkavagu stream of river Godavari, Hyderabad is found 293 for algae, 39 for MI, and 335 for fish. Among PPs, in Indian rivers, the presence of caffeine is the most frequent, with algae at the highest level of risk (RQmax= 24.5). Broadly six PPs, including azithromycin, caffeine, diclofenac, naproxen, norfloxacin, and sulfamethoxazole are found above PNEC values in Indian rivers. The application of IGS and RHI in understanding and presenting the river health condition (RHC) through colored hexagons has been demonstrated for the river Ganga near Varanasi (India) as an example. Identification of critical indicator groups, based on IGS provides a scientific basis for planned intervention for river health restoration to achieve an acceptable category.

Spontaneous tooth exfoliation after trigeminal herpes zoster: a case series of an uncommon complication.

The most significant and debilitating complication of herpes zoster (HZ) is herpetic neuralgia that accompanies and may persist in 10-15% of all zoster patients, particularly those over 60 years of age. The described 3 cases had an uncommon complication of spontaneous tooth exfoliation after trigeminal HZ that rarely finds mention in dermatology literature.

Biosimilars: the 'future' of biologic therapy?

The introduction of a number of biologic therapies to the market has revolutionized therapeutics in dermatology. However, the patents protecting their manufacture are about to lapse, and follow-on generic products, known as biosimilars, are about to flood the pharmaceutical market. The 'biosimilars' are different from the generic products of conventional drugs in terms of efficacy, safety and immunogenicity. This awareness is essential for their proper prescription and the safety of patients. This article intends to serve as a primer for dermatologists in their understanding of biosimilars.

Systemic sclerosis sine scleroderma and calcinosis cutis: report of a rare case.

Systemic sclerosis sine scleroderma is a rare form of limited cutaneous scleroderma. These patients manifest without cutaneous involvement, but do not differ in its clinical or laboratory features and prognosis from classical systemic sclerosis. In the absence of cutaneous signs/symptoms, its diagnosis is delayed leading to morbidity. The exact prevalence of dystrophic calcification in systemic sclerosis sine scleroderma, though a feature of systemic sclerosis, is not known. Development of dystrophic calcification further aggravates patient's woes. This paper describes systemic sclerosis sine scleroderma in a 17-year-old girl diagnosed initially as seronegative juvenile rheumatoid arthritis. She developed progressively increasing disk-like masses of calcinosis over the gluteal regions, knee, elbow, and ankle joints fixed to the overlying skin associated with malaise, anorexia, and weight loss. There was no Raynaud's phenomenon, dysphagia, dyspnoea, sclerodermatous skin, sclerodactyly, telangectasias, or muscle tenderness/weakness. Digital pitted scars, elevated anticentromere antibody values, esophageal hypomotility, and fluffy calcification in subdermal soft tissues in gluteal regions and around wrist, hip, knees, heels, and ankle joints (without affecting the underlying structures) were detected. Therapy with diltiazem and magnesium/aluminum antacids was useful in resolving calcinosis.

Management of hyperlipidemias: an update.

The discovery of the key enzymes, receptors, and transporters in cholesterol biosynthesis has enabled us to assemble fragments of knowledge concerning lipids and lipoproteins into dynamic pathways, leading to the development of a multitude of lipid-lowering drugs. After a brief recapitulation of the pathways of cholesterol metabolism and the dermatologic manifestations of lipid derangement, we shall review drugs which modify intestinal cholesterol and bile-acid reabsorption, and hepatic lipoprotein biosynthesis and catabolism. The current literature is examined to determine future therapeutic targets in lipid metabolism, as well as the role of traditional foods as lipid-lowering agents. The latest National Cholesterol Education Program guidelines for managing hypercholesterolemia are also discussed.

The sandflies of the Satluj river valley, Himachal Pradesh (India): some possible vectors of the parasite causing human cutaneous and visceral leishmaniases in this endemic focus.

BACKGROUND & OBJECTIVES: The recently recognized endemic focus of leishmaniasis in Satluj river valley in Himachal Pradesh (India) lies in north-western Himalayas (30 degrees N, 70 degrees E). This endemic focus of leishmaniasis appears peculiar where localized cutaneous leishmaniasis (LCL) co-exists with visceral leishmaniasis (VL), and Leishmania donovani is predominant pathogen for LCL whereas only a few cases have been due to Leishmania tropica. This study was carried out to collect sandflies, identify and delineate their habitat and role in transmission of human leishmaniasis in this endemic focus. METHODS: During June 2003 to September 2007, 142 (M-22, F-120) sandflies were collected with aspirators from 10 endemic villages of Kinnaur and Shimla districts. RESULTS & CONCLUSION: Sixty-two of the identified sandflies caught belonged to the genus Phlebotomus species, including some species that are known to act as vectors of the parasites causing human leishmaniasis. The Phlebotomus (Adlerius) chinensis longiductus (Parrot), 1928 (28 sandflies), P. major (8 sandflies), P. (Larroussius) kandelakii burneyi (Lewis), 1967 (8 sandflies) were identified. The identification of the main species of vector sandfly in the region is complicated because it is still uncertain which Leishmania species cause(s) the local human leishmaniasis. Circumstantially it seems likely, however, that Phlebotomus (Adlerius) chinensis longiductus is the main vector. Other species found, such as P. major and P. (Larroussius) kandelakii burneyi, may also be responsible for some cases. A more elaborate study is recommended.

Ehlers-Danlos syndrome--vascular type (ecchymotic variant): cutaneous and dermatopathologic features.

Ehlers-Danlos syndrome - vascular type, the only lethal form, is rarely reported in dermatology literature. It is characterized by translucent, atrophic skin, easy bruising, arterial, intestinal and/or uterine fragility manifesting as varicose veins, aneurysms and vascular/visceral/uterine rupture. As its dermatopathologic features are not well elucidated, diagnosis is often made after a catastrophic complication or at autopsy. This 36 year-old non-consanguineous male had brown-black plaques with atrophy and frequent ulceration over legs and dorsal feet and tortuous varicose veins around ankles for the past 15 years. Perivenous skin was translucent and hypopigmented. He had multiple and ecchymotic keloids and small atrophic, pityriasis versicolor-like lesions over trunk. He did not have hypermobile/hyperextensible skin and joints and showed no systemic or investigative abnormality. Histopathologic features of atrophic lesion included blood extravasation in atrophic epidermis/dermis, focal clustering and dilatation of blood vessels, malformed vessel walls, abundant hemosiderin in the dermis and homogenously stained/whorled patterned collagen especially around blood vessels. Pathology of keloidal lesion showed new collagen and vascular fragility. These histopathologic features appear of diagnostic value especially in patients who have compatible clinical findings but cannot afford confirmation by biochemical testing for abnormal synthesis of type III procollagen or identification of mutations in the COL3A1 gene.

Isolation of Sporothrix schenckii from the environmental sources of cutaneous sporotrichosis patients in Himachal Pradesh, India: results of a pilot study.

Himachal Pradesh, India is a known endemic area for cutaneous sporotrichosis. No attempt has been made to isolate Sporothrix schenckii, the causative fungus, from environmental sources in this region or in India as such. This prospective study was carried out to isolate Sporothrix schenckii from different environmental samples collected from the vicinity of cutaneous sporotrichosis patients. All patients of cutaneous sporotrichosis diagnosed during March 2005-February 2006 were studied. Twenty-one biopsy specimens and 62 environmental samples of soil, various thorns, corn-stalk, grass-blades and sphagnum moss were subjected to mycologic culture on Sabouraud's glucose agar. Sporothrix schenckii was identified by colony characteristics, lacto-phenol cotton blue mounts and demonstration of temperature dimorphism. These patients (F : M 15 : 6) were between 12 and 72 years of age and had cutaneous lesions for 45 days to 4 years. Lymphocutaneous and fixed cutaneous sporotrichosis was seen in 14 (66.6%) and 7 (33.3%) patients respectively. Extremities were involved in 16 (76.2%); and 5 (23.8%) patients had facial lesions. Ten (47.4%) biopsy specimens and six environmental (three soil, three corn-stalk) samples were culture-positive, which showed morphological characteristics suggesting Sporothrix schenckii. No variation in colony characteristics and mycelial morphology was observed in growth isolates from clinical or environmental samples. Temperature dimorphism was observed in all the 10 isolates obtained from the clinical specimens and in two isolates cultured from corn-stalk. Corn-stalks are evidently important sources of Sporothrix schenckii infection although subsequent contamination of wounds appears more important for development of clinical disease. Culture of Sporothrix schenckii from environmental sources may not be always possible to correlate with profile of injuries.

Methotrexate versus hydroxycarbamide (hydroxyurea) as a weekly dose to treat moderate-to-severe chronic plaque psoriasis: a comparative study.

BACKGROUND: Literature is replete with reports on the therapeutic efficacy and toxicity of methotrexate or hydroxycarbamide for treating chronic plaque psoriasis but no comparative study on their efficacy/safety has been carried out. While methotrexate has long been used in weekly doses in the treatment of psoriasis, the efficacy of hydroxycarbamide as a weekly therapy remains universally unexplored. METHODS: Two groups of 15 patients each having moderate-to-severe chronic plaque psoriasis were given weekly doses of methotrexate (15-20 mg/week) or hydroxycarbamide (3-4.5 g/week). The clinical response was assessed by the percentage reduction in the baseline PASI scores for the next 12 weeks. RESULTS: At the end of 12 weeks, the mean percentage reduction in the PASI score was 77.28+/-18.80 in the methotrexate group and 48.47+/-26.53 in the hydroxycarbamide group. Ten (66.66%) patients in the methotrexate group achieved >75% reduction in the PASI score, while in the hydroxycarbamide group only two (13.33%) patients showed similar results, signifying that methotrexate leads to a faster clearance of the disease. The methotrexate-related side effects, however, were also higher. CONCLUSIONS: Weekly doses of hydroxycarbamide can be used as an alternative to methotrexate in patients who either experience intolerable methotrexate side effects or have achieved its recommended cumulative dose.

Thalidomide: an experience in therapeutic outcome and adverse reactions.

BACKGROUND: The US FDA-approved thalidomide for the treatment of chronic recurrent/severe erythema nodosum leprosum. Thalidomide is also useful in many other inflammatory dermatological conditions where patients have exhausted other treatment options. METHODS: The beneficial and adverse clinical effects of thalidomide were studied in 25 patients suffering from different inflammatory dermatological conditions that were poorly controlled with conventional therapies. RESULTS: Thalidomide was found to be effective in various inflammatory dermatological diseases other than chronic recurrent erythema nodosum leprosum such as Behçet's disease, disseminated and hypertrophic discoid lupus erythematosus, erosive lichen planus, discoid lupus erythematosus-lichen planus overlap, recurrent aphthous stomatitis and prurigo nodularis. Deep vein thrombosis due to thalidomide occurred in 20% of these patients and appears to be a significant side effect. CONCLUSION: Thalidomide appears promising in a number of inflammatory dermatological conditions and will probably find new usages in future. The treating physicians need to be wary of the thrombo-embolic complications due to thalidomide especially when glucocorticoids or other chemotherapeutic agents such as doxorubicin, gemcitabine, 5-fluorouracil or dexamethasone-cyclophosphamide pulse therapy are being used concomitantly, and in patients of metastatic renal carcinoma, myelodysplastic syndrome or multiple myeloma receiving thalidomide/chemotherapy. Antiphospholipid or anticardiolipin antibodies appear to be other possible risk factors for this complication.

Comparative efficacy of intralesional sodium stibogluconate (SSG) alone and its combination with intramuscular SSG to treat localized cutaneous leishmaniasis: Results of a pilot study.

BACKGROUND: Intralesional sodium stibogluconate (SSG) has become first line therapy for localized cutaneous leishmaniasis (LCL). AIMS: This study compares the efficacy of intralesional SSG given alone with that of intralesional SSG combined with intramuscular SSG. METHODS: Thirty-two patients aged between 5-56 years were included in the study. The first group received three injections of intralesional SSG on alternate days while the other group received three injections of intralesional SSG similar to the first group and the rest of the calculated dose as a simultaneous, intramuscular injection. Patients were followed up every four weeks to assess for cure/ the need for repeating the treatment. RESULTS: Five patients from group 1 having small nodular lesions of < six months duration were cured after 1-2 treatment cycles. However, six patients with mucosal lesions, large lesions and lesions of > six months duration needed 3-5 treatment schedules. Most plaques and mucosal lesions in seven patients in group 2 cleared with two treatment cycles. CONCLUSION: Intralesional combined with intramuscular SSG appears more effective in LCL and gave qualitatively superior healing than intralesional SSG given alone.

Acrokeratosis paraneoplastica (Bazex syndrome): case report and review of literature.

Acrokeratosis paraneoplastica of Bazex is a rare syndrome. This condition is a distinct skin marker of supra-diaphragmatic neoplasia. This syndrome is important because the cutaneous findings preceed the onset of symptoms referable to the underlying neoplasm by several months in majority of the cases. We report here a case of a 63-year-old cachectic female who had classic psoriasiform lesions of acrokeratosis of Bazex with underlying bronchogenic carcinoma of the right lung.