Hepatitis A outbreak in Hulu Langat District, Selangor State, Malaysia during April--October 2002

A Hepatitis A outbreak occurred in Mukim Hulu Langat, Hulu Langat district from April 2002 to October 2002. Of the 51 cases notified, most were among students and the ethnic groups involved were Malays and the Orang Asli (local indigenous community). Epidemiological investigations revealed that the cases were localized along rivers used for recreational activities in this area. River water analysis indicated human faecal contamination and it was believed that the contamination was due to the Orang Asli community living upstream. This occurred due to lack of toilet facilities, water at point of use and the existing traditional practices of the Orang Asli community. Control measures instituted were intense health education to the Orang Asli to avoid using the rivers for defecation, multi agency efforts to provide sanitary toilets and adequate water to the villages affected. Future measures include conducting a sero- prevalence survey to determine the feasibility of Hepatitis A immunization to the susceptible population in this area. The outbreak that began in April 2002 was controlled by October 2002.     

Severe hypersensitivity pneumonitis associated with anagrelide

OBJECTIVE: To report a case of severe life-threatening hypersensitivity pneumonitis temporally associated with the use of anagrelide in a patient with myeloproliferative disorder. CASE SUMMARY: A 60-year-old white woman with chronic myeloid leukemia who had been treated with hydroxyurea for 7 years was offered anagrelide to control thrombocytosis. She developed severe hypersensitivity pneumonitis soon after the drug was initiated and required intubation and mechanical ventilation. A high-resolution computed tomography scan of the chest demonstrated extensive multifocal ground glass attenuation and patchy alveolar consolidation involving both lungs. Bronchoalveolar lavage revealed a preponderance of lymphocytes, suggesting hypersensitivity phenomenon, but was otherwise negative for malignancy and other causes of interstitial pneumonitis. An objective causality assessment revealed that an adverse drug event was probable. Discontinuation of anagrelide and hydroxyurea, and institution of corticosteroid therapy resulted in dramatic improvement. DISCUSSION: To our knowledge, this is the first case report of severe hypersensitivity pneumonitis closely related to anagrelide therapy. Pulmonary infiltrates have rarely been noted in patients treated with anagrelide. Anagrelide does not depress white blood cell production, causes mild anemia, and is devoid of the leukemogenic potential characteristic of radioactive phosphorus and other alkylating agents. Common adverse effects to anagrelide include headache, nausea, diarrhea, peripheral edema, and palpitations. Frank congestive heart failure and cardiomyopathy have occurred in a small number of patients, but severe pulmonary adverse effects have not emerged as a frequent problem. CONCLUSIONS: Vigilance is advised in patients who develop dyspnea while taking anagrelide and hydroxyurea. Healthcare providers need to be aware of the possibility of the development of serious life-threatening hypersensitivity pneumonitis. These patients may benefit from serial chest X-rays, pulmonary function testing, and echocardiography.     

Hesperetin induces an apoptosis-triggered extrinsic pathway and a p53- independent pathway in human lung cancer H522 cells

We studied the chemoprevention property of hesperetin on H522 cells using MTT, an apoptosis assay, an analysis of cell cycle progression, and the mitochondrial membrane potential, and apoptotic marker gene expression was determined using quantitative PCR. Hesperetin enhanced apoptotic cell death and mitochondrial membrane potential loss in H522 cells. Hesperetin up-regulated the levels of Fas, FADD, and caspase-8 expression and downregulted the levels of caspase-3 and caspase-9, p53, and Bax expression in H522 cells. This study shows that hesperetin induces apoptosis in H522 cells via a pathway independentof p53 and Bax but triggers the death-receptor Fas-initiated FADD/ caspase-8-dependent apoptotic pathway.     

Antimicrobial Activity and Phytochemical Constituents of Leaf Extracts of Cassia auriculata

Plants produce a wide variety of phytochemical constituents, which are secondary metabolites and are used either directly or indirectly in the pharmaceutical industry. ‘For centuries, man has effectively used various components of plants or their extracts for the treatment of many diseases, including bacterial infections. In the present study methanol, chloroform and aqueous extracts of Cassia auriculata leaf were subjected for antimicrobial activity by well-diffusion method against six bacterial strains namely Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. The results revealed that the methanol and chloroform extracts exhibited strong inhibitory activity against all the tested organisms (zone of inhibition of 12-20 mm), except Pseudomonas aeruginosa (zone of inhibition 10 mm or nil). The aqueous extracts showed moderate activity by ‘Zone of inhibition ≤12 or nil). The extracts were screened for their phytochemical constituents by standard protocols’ and were shown to contain carbohydrates, proteins, alkaloids, flavonoids, steroids, saponins and tannins. The antibacterial activity of these extracts is possibly linked to the presence of flavonoids, steroid, saponins and/or tannins. Further studies are needed to determine the precise active principles from Cassia auriculata.     

Lycopersene: A review on extraction,identification and purification and applications

Lycopersene is a stable and safe triterpenoid. Lycopersen had utilized as an antioxidant, antimutagenic, antiproliferative, cytotoxicity, antibacterial and pesticide. Obtaining pure Lycopersene from natural sources is very important for fundamental research and the above applications. The present overview provides an up-to-date and comprehensive summary of the various methods used for extraction, isolation and purification of Lycopersene from natural sources with its applications in food, cosmetics and pharmaceutical fields. Many different extraction methods ranging from conventional techniques (e.g. Soxhlet extraction, Maceration and Rotary evaporator) and other advanced extraction technologies (e.g. Solid-phase microextraction, steam distillation with Clevenger, Clevenger apparatus, Chromatography on SiO₂ column, centrifuge, sonication) had been used to obtain Lycopersene from flora and fauna. Purification techniques, alone or in combination, have been investigated for isolation and purification of Lycopersene from crude extracts in various natural sources. The review of Lycopersene identified cap areas like purity and application in various fields.     

Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4-oxidative stress cascade

BACKGROUND AND PURPOSE

Boldine is a potent natural antioxidant present in the leaves and bark of the Chilean boldo tree. Here we assessed the protective effects of boldine on endothelium in a range of models of diabetes, ex vivo and in vitro.

EXPERIMENTAL APPROACH

Vascular reactivity was studied in mouse aortas from db/db diabetic and normal mice. Reactive oxygen species (ROS) production, angiotensin AT₁ receptor localization and protein expression of oxidative stress markers in the vascular wall were evaluated by dihydroethidium fluorescence, lucigenin enhanced-chemiluminescence, immunohistochemistry and Western blot respectively. Primary cultures of mouse aortic endothelial cells, exposed to high concentrations of glucose (30 mmol L⁻¹) were also used.

KEY RESULTS

Oral treatment (20 mg kg⁻¹day⁻¹, 7 days) or incubation in vitro with boldine (1 μmol L⁻¹, 12 h) enhanced endothelium-dependent aortic relaxations of db/db mice. Boldine reversed impaired relaxations induced by high glucose or angiotensin II (Ang II) in non-diabetic mouse aortas while it reduced the overproduction of ROS and increased phosphorylation of eNOS in db/db mouse aortas. Elevated expression of oxidative stress markers (bone morphogenic protein 4 (BMP4), nitrotyrosine and AT₁ receptors) were reduced in boldine-treated db/db mouse aortas. Ang II-stimulated BMP4 expression was inhibited by boldine, tempol, noggin or losartan. Boldine inhibited high glucose-stimulated ROS production and restored the decreased phosphorylation of eNOS in mouse aortic endothelial cells in culture.

CONCLUSIONS AND IMPLICATIONS

Boldine reduced oxidative stress and improved endothelium-dependent relaxation in aortas of diabetic mice largely through inhibiting ROS overproduction associated with Ang II-mediated BMP4-dependent mechanisms.     

Isolation and Characterisation of Degradation Impurities in the Cefazolin Sodium Drug Substance

Two unknown impurities were detected in the cefazolin sodium bulk drug substance using gradient reversed-phase high-performance liquid chromategraphy (HPLC). These impurities were isolated by preparative HPLC and characterized by using spectroscopic techniques like LC-MS, LC-MS/MS, 1D, 2D NMR, and FT-IR. Based on the spectral data, the impurities have been characterized as N-(2,2-dihydroxyethyl)-2-(1H-tetrazol-1-yl)acetamide (Impurity-I) and 2-{carboxy[(1H-tetrazol-1-ylacetyl)amino]methyl}-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid (Impurity-II). The structures of these impurities were also established unambiguously by co-injection into HPLC to confirm the retention time. To the best of our knowledge, these two impurities were not reported elsewhere.     

Sesame Oil Therapeutically Ameliorates Cardiac Hypertrophy by Regulating Hypokalemia in Hypertensive Rats

Background: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long‐term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. Methods: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K⁺ and Mg²⁺ levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. Results: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K⁺ and Mg²⁺ while limiting the urinary excretion of K⁺ in DOCA/salt‐induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. Conclusion: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.