New bithiophene derivative attenuated Alzheimer's disease induced by aluminum in a rat model via antioxidant activity and restoration of neuronal and synaptic transmission.

BACKGROUND: One of the hypotheses that leads to an increased incidence of Alzheimer's disease (AD) is the accumulation of aluminum in the brain's frontal cortex. The present study aimed to evaluate the therapeutic role of a novel bithiophene derivative at two doses against AlCl3-induced AD in a rat model. METHODOLOGY: Adult male rats were divided into six groups, 18 rats each. Group 1: naïve animals, group 2: animals received a daily oral administration of bithiophene dissolved in DMSO (1 mg/kg) for 30 days every other day, groups 3-6: animals received a daily oral administration of AlCl3 (100 mg/kg/day) for 45 consecutive days. Groups 4 and 5 received an oral administration of low or high dose of the bithiophene (0.5 or 1 mg/kg, respectively). Group 6; Animals were treated with a daily oral dose of memantine (20 mg/kg) for 30 consecutive days. MAIN FINDINGS: Al disturbed the antioxidant milieu, elevated the lipid peroxidation, and depleted the antioxidants. It also disturbed the synaptic neurotransmission by elevating the activities of acetylcholine esterase and monoamine oxidase resulting in the depletion of dopamine and serotonin and accumulation of glutamate and norepinephrine. Al also deteriorated the expression of genes involved in apoptosis and the production of amyloid-ß plaques as well as phosphorylation of tau. The new bithiophene at the low dose reversed most of the previous deleterious effects of aluminum in the cerebral cortex and was in many instances superior to the reference drug; memantine. CONCLUSION: Taking together, the bithiophene modulated the AD etiology through antioxidant activity, prevention of neuronal and synaptic loss, and probably mitigating the formation of amyloid-ß plaques and phosphorylation of tau.

Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea.

AIMS: Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD). METHODS: We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender. RESULTS: Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P < 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2-1.95, P = 0.05 was significantly associated with CDAD. CONCLUSIONS: This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.

Vermicompost Supply Modifies Chemical Composition and Improves Nutritive and Medicinal Properties of Date Palm Fruits From Saudi Arabia.

To meet the increased demand for phytochemicals, plant cultivation in soil amended with biofertilizers has been developed. Here, we aimed to use vermicompost as an environmentally safe biofertilizer to enhance the nutritive and medicinal value of five common cultivars of Saudi date palm; namely Phoenix dactylifera L. var. Ajwa, Hulwa, Ruthana, Sefri, and Luban. To determine changes in the fruit nutritive composition, primary metabolites, antioxidants, phenolic compounds and mineral profiles were analyzed in the fruits from non-fertilized and vermicompost-fertilized date palms. We also tested how changes in the fruit chemical compositions due to vermicompost fertilization affected their medicinal potentials. Applying vermicomposts generally increased primary metabolites, vitamins, and mineral content as well as the medicinal potential of the date palm fruits. This positive effect is possibly explained by the role of vermicomposts in improving soil health and fertility. Furthermore, clustering analyses and principal component analysis (PCA) indicated cultivar-specific responses. PCA analysis also revealed that the bioactivities of the date palm fruit extracts and their antioxidants tended to display correlated output values. One of the highly accumulated phenolic compounds, ß-D-glucogallin, was extracted and purified from P. dactylifera L. var. Ajwa fruits and showed significant antioxidant, anticancer, antibacterial, antimutagenic, and antiprotozoal activities. Overall, applying vermicompost is an innovative approach to increase the nutritive quality and medicinal potential of date palm fruits.

Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population.

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

Computerised image analysis of vitiligo lesion: evaluation using manually defined lesion areas.

BACKGROUND: Vitiligo is a cutaneous pigmentary disorder characterized by depigmented macules and patches that result from loss of epidermal melanocytes. Physician evaluates the efficacy of treatment by comparing the extent of vitiligo lesions before and after treatment based on the overall visual impression of the treatment response. This method is called the physician's global assessment (PGA) which is subjective. In this article, we present an innovative digital image processing method to determine vitiligo lesion area in an objective manner. METHOD: The digital method uses Independent Component Analysis (ICA) to generate melanin-based images representing skin areas due to melanin followed by Region Growing process to segment vitiligo lesion from normal skin. RESULTS: Based on 41 digital images of vitiligo lesions taken from 18 patients, the proposed method achieved sensitivities of 0.9105 ± 0.0161, specificities of 0.9973 ± 0.0009 and accuracies of 0.9901 ± 0.0028 at 95% confidence level. CONCLUSION: With the proposed method, physicians are able to assess vitiligo treatment efficacies objectively.

Objective assessment of psoriasis erythema for PASI scoring.

Skin colour is vital information in dermatological diagnosis as it reflects the pathological condition beneath the skin. It is commonly used to indicate the extent of diseases such as psoriasis, which is indicated by the appearance of red plaques. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to determine severity of psoriasis lesion. Erythema (redness) is one parameter in PASI and this condition is assessed visually, thus leading to subjective and inconsistent results. Current methods or instruments that assess erythema have limitations, such as being able to measure erythema well for low pigmented skin (fair skin) but not for highly pigmented skin (dark skin) or vice versa. In this work, we proposed an objective assessment of psoriasis erythema for PASI scoring for different (low to highly pigmented) skin types. The colour of psoriasis lesions are initially obtained by using a chromameter giving the values L*, a*, and b* of CIELAB colour space. The L* value is used to classify skin into three categories: low, medium and highly pigmented skin. The lightness difference (DeltaL*), hue difference (Deltah(ab)), chroma (DeltaC*(ab)) between lesions and the surrounding normal skin are calculated and analysed. It is found that the erythema score of a lesion can be distinguished by their Deltah(ab) value within a particular skin type group. References of lesion with different scores are obtained from the selected lesions by two dermatologists. Results based on 38 lesions from 22 patients with various level of skin pigmentation show that PASI erythema score for different skin types i.e. low (fair skin) to highly pigmented (dark skin) skin types can be determined objectively and consistent with dermatology scoring.

Area assessment of psoriasis lesions for PASI scoring.

Psoriasis is a skin disorder which is caused by a genetic fault. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, the current gold standard method, PASI (Psoriasis Area and Severity Index), is used to measure psoriasis severity by evaluating the area, erythema, scaliness and thickness of the plaques. However, the determination of PASI can be tedious and subjective. In this work, we develop a computer vision method that determines one of the PASI parameters, the lesion area. The method isolates healthy and healed skin areas from lesion areas by analysing the hue and chroma information in the CIE L*a*b* colour space. Centroids of healthy skin and psoriasis in the hue-chroma space are determined from selected sample. The Euclidean distance of all pixels from each centroid is calculated. Pixels are assigned to either healthy skin or psorasis lesion classes based on the minimum Euclidean distance. The study involves patients from different ethnic origins having three different skin tones. Results obtained show that the proposed method is able to determine lesion areas with accuracy higher than 90% for 28 out of 30 cases.

Cutaneous vasculitis: a review of aetiology and clinical manifestations in 85 patients in Malaysia.

Cutaneous vasculitis presents with a variety of clinical morphologies and causes significant morbidity. A total of 85 patients with cutaneous vasculitis at Hospital Kuala Lumpur were retrospectively reviewed. Palpable purpura was seen in 49.4% and frequently involved the lower limbs (50.6%). Identifiable causes include drugs (28.2%), infections (20.0%) and connective tissue disorders (16.5%). Non steroidal antiinflammatory were the commonest group of drugs responsible for 25% of cases while B-haemolytic streptococci was the leading infectious cause (64.7%).

A novel therapy for the treatment of pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is an uncommon, chronic, painful, ulcerative skin disease of unknown origin, often associated with systemic diseases including inflammatory bowel disease, rheumatoid arthritis; monoclonal gammopathy, hepatitis and myeloproliferative disorders. The mainstay of therapy for PG has been high-dose corticosteroids but not all patients have a favourable outcome. Other systemic agents have also been used such as cyclosporine, azathioprine, cyclophosphamide and tacrolimus. However, all these systemic therapies can be complicated by serious side effects. In this paper, we report a series of four patients with pyoderma gangrenosum treated successfully with topical cyclosporine. No side-effects were observed in any of the patients and there was minimal systemic absorption of the topical cyclosporine.

Malaysian Psoriasis Registry--preliminary report of a pilot study using a newly revised registry form.

The Malaysian Psoriasis Registry, established in 1998, is the first skin disease clinical registry in Malaysia. It aims to provide useful data on various aspects of psoriasis. Following an extensive revision of the registry form in 2007, a total of 509 psoriasis patients from 10 government dermatologic centres were reviewed in a three month pilot study. The onset of psoriasis was during the second to fourth decade of life in the majority of patients. There was no sexual and ethnic predilection. A positive family history was present in 21.2%, and more common in patients with younger disease onset. The main aggravating factors of psoriasis were stress, sunlight and infection. Plaque psoriasis was the commonest clinical type (80.9%). Joint disease was present in 17.3% of patients, among which mono-/oligoarticular type being the commonest. Nail changes occurred in 68%. More psoriasis patients were overweight and obese compared to the normal population. The mean Dermatologic Life Quality Index (DLQI) score was 8.08 +/- 6.29, and changes during subsequent follow-up may reflect therapeutic effectiveness. This study enabled evaluation of the revised registry form and helped in identifying shortcomings in the implementation of the registry.

Objective assessment of psoriasis erythema for PASI scoring.

Skin colour is vital information in dermatological diagnosis. It reflects pathological condition beneath the skin and commonly being used to indicate the extent of a disease. Psoriasis is a skin disease which is indicated by the appearance of red plaques. Although there is no cure for psoriasis, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, PASI (Psoriasis Area and Severity Index) which is the current gold standard method is used to determine severity of psoriasis lesion. Erythema (redness) is one parameter in PASI. Commonly, the erythema is assessed visually, thus leading to subjective and inconsistent result. In this work, we proposed an objective assessment of psoriasis erythema for PASI scoring. The colour of psoriasis lesion is analyzed by DeltaL, Deltahue, and Deltachroma of CIELAB colour space. References of lesion with different scores are obtained from the selected lesions by two dermatologists. Results based on 38 lesions from 22 patients with various level of skin pigmentation show that PASI erythema score can be determined objectively and consistent with dermatology scoring.

Area assessment of psoriasis lesion for PASI scoring.

Psoriasis is a skin disorder which is caused by genetic fault. There is no cure for psoriasis, however, there are many treatment modalities to help control the disease. To evaluate treatment efficacy, PASI (Psoriasis Area and Severity Index) which is the current gold standard method is used to measure psoriasis severity by evaluating the area, erythema, scaliness and thickness of the plaques. However, the calculation of PASI can be tedious and subjective. In this work, we develop a computer vision method that determines one of the PASI parameter, the lesion area. The method isolates healthy (or healed) skin areas from lesion areas by analyzing the hue and chroma information in the CIE L*a*b* colour space. Centroids of healthy skin and psoriasis in the hue-chroma space are determined from selected sample. Euclidean distance of all pixels from each centroid is calculated. Each pixel is assigned to the class with minimum Euclidean distance. The study involves patients from three different ethnic origins having different skin tones. Results obtained show that the proposed method is comparable to the dermatologist visual approach.

Subcutaneous panniculitic T-cell lymphoma-review of five cases.

Subcutaneous panniculitic T-cell lymphoma (SPTL) is a rare variant of cutaneous T-cell lymphoma where lymphoma cells infiltrate preferentially into subcutaneous tissue. Five cases of SPTL were seen during the period from 2001-2004 at the Department of Dermatology, Hospital Kuala Lumpur. All five presented with multiple subcutaneous nodules on the face, trunk and limbs of one week to six months duration with associated fever and loss of weight. Physical examination showed multiple tender, erythematous indurated plaques and subcutaneous nodules on their face, trunk and limbs. One patient also presented with unhealing ulcerated nodules. Two patients had hepatosplenomegaly and one hepatomegaly. Two patients had pancytopaenia while the other three had leucopaenia. One patient had deranged liver function. Out of the five patients, three had bone marrow examination with haemophaegocytosis in two and one hypocellular marrow. Skin biopsy of all patients showed infiltration with atypical lymphoid cells in the upper dermis and subcutaneous fat. These neoplastic cells showed positivity for CD3 and CD30 in three patients with CD8, TIA-1 and LCA (Leucocyte common antigen) being positive in one patient. One patient treated with prednisolone and subcutaneous Roferon 3Mu three times a week since 2001 was in remission. Two patients who were planned for chemotherapy had deteriorated rapidly and succumbed to septicaemia from pancytopaenia. Subcutaneous panniculitic T-cell lymphoma has been reported to show two distinct clinical presentations. The first is characterized by an indolent course with good prognosis and the second with rapid clinical deterioration, haemophaegocytosis and death. Both presentations were seen in our five patients seem to demonstrate these two subtypes of SPTL.

Urethritis in men at the Genito-Urinary Medicine Clinic Kuala Lumpur Hospital.

The clinical features and aetiology of 100 consecutive symptomatic heterosexual male patients with urethritis were studied from March 1994 to August 1994 in the Genito-Urinary Medicine (GUM) Clinic, Kuala Lumpur Hospital. Gonococcal urethritis (GU) was found to be more common (53%) than non-gonococcal urethritis(47%). All patients with GU confirmed microbiologically had clinically evident urethral discharge. Almost half (41%) of the patients with GU developed post-gonococcal urethritis (PGU). The most common organism isolated in PGU was Ureaplasma urealyticum (37%) whilst only 4% had both Chlamydia trachomatis and Ureaplasma urealyticum. Of the 47% of patients with non-gonococcal urethritis (NGU), 50% had no microorganism isolated, 32% had Ureaplasma urealyticum, 7% Chlamydia trachomatis and 11% both Chlamydia trachomatis and Ureaplasma urealyticum.

Onchocerca gutturosa infection of the ligamentum nuchae in two cows in the Sudan.

Severe lesions of the ligamentum nuchae are described for the first time in two cows in the Sudan. Post mortem and histopathological examination of the nodules reveals inflammatory process the causal agent of which is Onchocerca gutturosa.

Chronic mucocutaneous candidiasis with deficient CD2 (E receptor) but normal CD3 mononuclear cells.

A case of chronic mucocutaneous candidiasis in a Malaysian child who subsequently developed disseminated tuberculosis and toxoplasmosis is described. The phenotype of her peripheral blood mononuclear cells showed discordance for her T cell markers. The presence of a subpopulation of CD2-/CD3+ mononuclear cells leading to an immunodeficiency state is consistent with failure of activation of CD2-mediated alternative pathway resulting in immunodeficiency. Such abnormal CD2-/CD3+ subpopulations have been described in lepromatous leprosy and foetal abortuses.

Synthesis and antiviral evaluation of 6-p-ethylphenyl-5H-pyrrolo [3,4-b]pyridine-5,7-dione.

The synthesis of 6-(p-ethylphenyl)-5H-pyrrolo [3,4-b]pyridine-5,7-dione is described. The compound has been studied for its in vitro activity on RNA-containing influenza viruses types A and B. The preliminary results indicate that the compound has a significant antiviral activity against influenza viruses types A and B at concentrations at which no cytotoxic effects on MRC-5 cells in tissue culture are present.