Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

Hearing impairment and hearing aid usage in Singapore

Objective: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore. Design: Retrospective cross-sectional study. Study sample: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013. Results: Mean age was 70?years with 50.8% male. Mean hearing loss (HL) was 63.1?dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. “Behind-the-Ear” HAs were cheaper than “In-Ear” HAs. Standard “Behind-The-Ear” HAs were also cheaper than “Receiver-in-Canal” HAs. Among In-Ear HAs, “In-the-Canal” and “Completely-in-Canal” were more popular than “In-the-Ear” HAs despite costing more. HA was used ≥4?days/week by 85.6% but >7?h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7?h of daily HA usage were predictors of successive HA fitting. Conclusions: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients' motivation, hearing disability, and HA effectiveness.     

Angiopoietins as promising biomarkers and potential therapeutic targets in brain injury

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, and enormous economic costs to society. The full spectrum of neurological damage created by TBI or SAH is not usually manifested at the time of injury, but evolves gradually over the course of hours to days (or weeks) following these injuries. Angiopoietins, important regulators of vascular structure and function, are hallmark indicators of vascular injury and may therefore represent promising targets in the treatment of SAH and TBI. In animal models and human tissues, normal intracerebral and pial vessels show strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and appear to contribute to the remarkable loss of blood–brain barrier (BBB) in these injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may provide new therapeutic modalities which can modify ‘secondary’ forms of brain injury after TBI and SAH.     

Melioidosis in India and Bangladesh: A review of case reports

Objective: To conduct an epidemiological and clinical review of published case reports of melioidosis from India and Bangladesh. Methods: Data from published case reports were abstracted and summarized. We further compared the clinical epidemiology of the melioidosis cases in India with case series from highly endemic areas in Northern Australia and Southeast Asia to elucidate any differences in presentations and risk factors between the regions.Results: We identified a total of 99 cases published between 1953 and June 2016, originating from India(n=85) or Bangladesh(n=14). Cases were predominantly male and ranged in age from 1 month to 90 years. Diabetes mellitus was the most common risk factor reported(58%). About 28% of the cases had history of exposure via high-risk occupations or exposure to contaminated water. The overall case fatality rate(CFR) was 26%. Factors influencing mortality included the occurrence of septic shock(CFR, 80%), environmental exposure(CFR,39%), primary presentation of pneumonia(CFR, 38%), misdiagnosed and/or mistreated cases(CFR, 33%) or the presence of a risk factor(CFR, 29%). Because of the small number of cases in Bangladesh, pattern of clinical epidemiology is limited to India. Soft tissue abscess(37%)was the most common clinical presentation reported from India followed by pneumonia(24%)and osteomyelitis/septic arthritis(18%). Neurological melioidosis(n=10, 12%) presented as pyemic lesions of the brain or meninges. A few cases of prostatic abscess(n=4) in men and parotid abscess(n=4) were also noted. The above patterns were consistent with case series from Southeast Asia and Northern Australia for the most part, in terms of risk factors associated with infection and factors influencing mortality. Differences included clinical presentation of pneumonia which was notably lower than that reported in Southeast Asia and Northern Australia; a higher proportion of neurological and parotid abscess presentation; and a lower CFR compared to that reported in case series in Southeast Asia. About 39% of the cases were misdiagnosed and/or mistreated, suggesting underreporting and under estimation of the true disease burden. Conclusions: The concentration of melioidosis cases in southern and eastern states in India and in Bangladesh, which share climatic conditions and rice farming activities with known endemic areas in Southeast Asia, suggests an endemicity of melioidosis in this region. Thus, increased awareness among healthcare personnel, particularly among clinicians and nurses practicing in rural areas, and improved surveillance through case registries is essential to guide early diagnosis and prompt treatment.     

Conjunctival melanoma in a child: A clinicopathological report

We report a case of a 16 years old Asian Indian boy who presented with a large brownish lesion measuring 20 × 12 mm on the temporal conjunctive in his right eye. Anterior segment optical coherence topography revealed cystic spaces without scleral involvement. The patient underwent conjunctival excisional biopsy using “no touch” technique with double freeze-thaw cryotherapy to underside of the adjacent conjunctival margins. Excision involved 4 mm of the surrounding apparently normal conjunctiva. Absolute alcohol epitheliectomy was done at the limbus and surrounding 2 mm of cornea to devitalize residual atypical melanocytes if any. Histopathology confirmed diagnosis of conjunctival melanoma. We started the patient on topical mitomycin C 0.04% with one weekly on and off cycles postoperatively. No recurrence was noted after nine months follow up.