Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Immunostimulant Activity of Picroliv, the Iridoid Glycoside Fraction of Picrorhiza kurroa, and its Protective Action against Leishmania donovani Infection in Hamsters1

Picroliv, a standardised fraction from root and rhizome of Picrorhiza kurroa, consisting of iridoid glycosides and shown to be responsible for its hepatoprotective activity, was studied for immunostimulant activity. Oral administration of Picroliv (10 mg/kg x 7 days) in mice prior to immunization with sheep red blood cells (SRBC) resulted in a significant increase in haemagglutinating antibody (HA) titre, plaque forming cells (PFC), and delayed hypersensitivity (DTH) response to SRBC. Picroliv enhanced the non-specific immune response characterized by an increase in macrophage migration index (MMI), [14C]-glucosamine uptake, phagocytosis of [14C]-leucine labelled Escherichia coli, chemiluminescence of peritoneal macrophages, and higher uptake of [3H]-thymidine in the lymphocytes of treated mice. It also induced a high degree of protection in golden hamsters against challenge infection with Leishmania donovani promastigotes.     

Antileishmanial action of Tephrosia purpurea linn,extract and its fractions against experimental visceral leishmaniasis

Tephrosia purpurea (family: Fabaceae), which is used in traditional remedies for the treatment of febrile attacks, enlargement and obstruction of liver, spleen, and kidney, was found to have significant antileishmanial activity, and has been extensively fractionated to locate the abode of activity. A fraction (F062) obtained from N‐butanol extract of T. purpurea showed consistent antileishmanial activity at 50 mg/ kg × 5 days by oral route against Leishmania donovani infection in hamsters. Activity was further confirmed in a secondary model, i.e., Indian langur monkeys (Presbytis entellus). Thus, the fraction F062 from this plant possesses potential to produce significant antileishmanial activity by oral route without producing any toxic side effects. Drug. Dev. Res. 60:285–293, 2003. © 2003 Wiley‐Liss, Inc.     

Targets and management of hypertension in heart failure: focusing on the stages of heart failure

Hypertension is highly prevalent worldwide and is the major risk factor for heart failure (HF). More than half of the patients with HF in Asia suffer from hypertension. According to the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guideline, there are four stages of HF, including at risk for HF (stage A), pre‐HF (stage B), symptomatic HF (stage C), and advanced HF (stage D). Given the high prevalence of hypertension as well as HF and the stronger association between hypertension and cardiovascular diseases in Asians compared to the west, measures to prevent and alleviate the progression to clinical HF, especially controlling the blood pressure (BP), are of priority for Asian populations. After reviewing evidence‐based studies, we propose a BP target of less than 130/80 mmHg for patients at stages A, B, and C. However, relatively higher BP may represent an opportunity to maximize guideline‐directed medical therapy (GDMT), which could potentially result in a better prognosis for patients at stage D. Traditional antihypertensive drugs are the cornerstones for the management of hypertension at stages A and B. Notably, calcium channel blockers (CCBs) are inferior to other drug classes for the preventing of HF, whereas diuretics are superior to others. For patients at stage C, GDMT is essential which also helps the control of BP. In particular, sodium‐glucose cotransporter‐2 (SGLT2) inhibitors are newer therapies recommended for the treatment of HF and presumably even in hypertension to prevent HF. Regarding patients at stage D, GDMT is also recommended if tolerable and measures should be taken to improve hemodynamics.     

Hypertension and stroke in Asia: A comprehensive review from HOPE Asia

Stroke is the primary cause of disability and vascular death worldwide, including Asia. Asian characteristics that differ from the West lead to higher stroke incidence. Stroke epidemiology studies in Asia have shown varying levels of mortality, incidence, prevalence, and burden of disease. Hypertension is the most prevalent risk factor found in Asia. Besides ethnicity that is associated with stroke incidence, both systolic blood pressure, diastolic blood pressure, and blood pressure variability are positively correlated with stroke incidence. Post‐stroke cognitive impairment is one of the sequelae that affect one‐third of stroke survivors and has become a significant public health concern that is often neglected despite its increasing prevalence. Therefore, it is very important to prevent recurrence by treating stroke optimally and effectively. Increasing awareness and treatment adherence to hypertension, the leading risk factor for stroke, became the main goal in several countries in Asia.     

Does Squatting Worsen Lower Limb Ischemia in Patients with Peripheral Arterial Disease?

Peripheral arterial disease (PAD) is an important cause of morbidity and mortality in the world affecting up to 20% in people over 70?years of age. The prevalence is increasing in India due to combined effects of increased life expectancy, increased tobacco smoking and increased prevalence of diabetes mellitus. The aim of the study was to examine the hypothesis whether squatting posture reduces blood flow to lower limbs resulting in worsening of symptoms of lower limb ischemia in patients with PAD. 10 patients with arterial disorders due to thromboangiitis obliterans (TAO), atherosclerosis and diabetic macro vascular disease were selected for patients and were compared with 10 healthy volunteers as controls. Clinical examination and duplex scan of posterior tibial artery (PTA) and dorsalis pedis artery (DPA) performed in standing and squatting position in a clinical environment. They were asked about symptoms of numbness, ischemic pain and the results were noted. Results were tabulated and analysed using Microsoft Excel?. Members in the control group complained of numbness of both the limbs after a period of 30?min on an average. In the patients group, members while squatting complained of numbness in the involved limb within 5?min. They complained of ischemic pain in the involved limb within 10?min and developed numbness in the opposite limb in within 15?min. Posterior tibial artery and dorsalis pedis artery pulsations disappeared for the entire duration of squatting in both groups as confirmed by duplex scanning. It may be recommended that patients with established peripheral vascular disease should avoid squatting position, even if it is for a very short period of time. It is desirable to advice such patients to use appropriate structures as supports which will allow them to work without squatting. This may also necessitate a change in occupation.