Thalassaemia-A global view.

The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care therapy includes regular transfusions to maintain a haemoglobin level of around 10 g/dL, together with iron chelation therapy to prevent iron overload. Novel therapies, bone marrow transplantation, and gene therapy are treatment options that are unavailable in many countries with stressed economies.

Changes in Smoking Behaviour and Home-Smoking Rules during the Initial COVID-19 Lockdown Period in Israel.

The COVID-19 pandemic has caused devastating impacts globally. To mitigate virus spread, Israel imposed severe restrictions during March-April 2020. An online cross-sectional survey was conducted in April 2020 among current and ex-smokers to explore changes in smoking behaviour and home-smoking rules during this period.

Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy.

Microtubules (MTs) are highly dynamic polymers that constitute the cellular cytoskeleton and play a role in multiple cellular functions. Variability characterizes biological systems and is considered a part of the normal function of cells and organs. Variability contributes to cell plasticity and is a mechanism for overcoming errors in cellular level assembly and function, and potentially the whole organ level.

Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder.

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease.

Balancing needs and means: the dilemma of the beta-cell in the modern world.

The insulin resistance of type 2 diabetes mellitus (T2DM), although important for its pathophysiology, is not sufficient to establish the disease unless major deficiency of beta-cell function coexists. This is demonstrated by the fact that near-physiological administration of insulin (CSII) achieved excellent blood glucose control with doses similar to those used in insulin-deficient type 1 diabetics. The normal beta-cell adapts well to the demands of insulin resistance.

Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping.

The aim of this study was to determine the effect of adoptive transfer of regulatory natural killer T (NKT) lymphocytes on the metabolic disorder in leptin-deficient ob/ob mice, which feature depletion and defective function of NKT and CD4 lymphocytes. Leptin-deficient ob/ob mice were subjected to transplantation of 1 x 10(6) of either ob/ob or wild-type-derived NKT lymphocytes, or to transplantation of either ob/ob or wild-type-derived splenocytes. The effect on hepatic fat content was measured by magnetic resonance imaging (signal intensity index) and histology, using the steatohepatitis grading scale.

Gender differences in sympathoadrenal activity in rats at rest and in response to footshock stress.

A comparison was made of the dynamics of sympathoadrenal activity in 11 age-matched male and female rats, under basal conditions and after exposure to footshock. Rats were prepared with indwelling catheters in the tail artery 24 h before the experiment. Measurements were made of plasma corticosterone (COR), norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting conditions, after transfer to the shock box (novelty) and at various times after footshock.

Effect of prenatal stress on plasma corticosterone and catecholamines in response to footshock in rats.

The effect of prenatal stress was investigated on the sympathoadrenal response to novelty and footshock by measuring the time course of the changes in circulating corticosterone (COR) catecholamines and their metabolites. Pregnant rats were subjected to noise and light stress, three times weekly on an unpredictable basis throughout gestation. When the male offspring of stressed rats (PS) and those of unstressed mothers (C) were 4.

Role of renal nerves in hemodynamic and natriuretic responses to saline in rabbits with impaired baroreflex sensitivity.

The hemodynamic and urinary Na+ excretory response to a 2.5-fold increase in NaCl by i.v.

Prenatal stress depresses immune function in rats.

The aim of the present study was to determine the effect of prenatal stress on immune function in rats. Pregnant rats were stressed by noise and light, three times weekly throughout pregnancy. Experiments were performed on male and female offspring aged 2 months.

Effect of prenatal stress on opioid component of exploration in different experimental situations.

Prenatal stress interferes with the expression of opioid systems in rats. The present study determined the effect of prenatal stress on the opioid-influenced component of exploratory behavior, defined as the difference between the behavior of vehicle-treated and naloxone-treated rats, in three novel situations previously shown to cause different degrees of arousal. Pregnant rats were stressed three times weekly on a random basis by noise and flashing lights.

Possible role of the cholinergic system and disease models.

Memory impairment associated with the loss of cortical cholinergic neurons in AD has stimulated the development of animal models based on blockade or destruction of these systems. Strategies include mechanical lesions, local injection of excitotoxic amino acids or ethylcholine aziridinium (AF 64A), which disrupt reference and working memory in rats, but lack specificity for cholinergic systems. Other models involving, reduction in cerebral blood flow and interference with oxidative metabolism of glucose, mimic those found in AD, and also interfere with working and long-term memory in the rat.

Role of experimental conditions in determining differences in exploratory behavior of prenatally stressed rats.

The effect of prenatal stress was determined on exploration in situations that induce different levels of fear. Dams (12) were stressed by noise and light thrice weekly on an unpredictable basis throughout pregnancy, and 12 controls were left undisturbed. The time spent by different groups of their adult offspring of both sexes in exploration was assessed during 4 min in a plus maze; large, well-lit open field (1), and open field (2) after prior exposure to a small, dark holebox.

Renal denervation prevents sodium retention and hypertension in salt-sensitive rabbits with genetic baroreflex impairment.

1. Rabbits with a genetic impairment in baroreflex control of heart rate become hypertensive on a high salt diet. The present study determined the effect of bilateral renal denervation on blood pressure and sodium balance after salt loading (four times normal intake; 28-36 mEq NaCl/day) in normotensive rabbits with high (Group I) and low (Group II) baroreflex sensitivity, respectively.

The pharmacotherapy of Alzheimer's disease based on the cholinergic hypothesis: an update.

Alzheimer's disease (AD) is a neurodegenerative disorder with impairment of cognitive function and personality. The synaptic loss, neuronal atrophy and degeneration of cholinergic nuclei in the basal forebrain may be associated with a reduction in oxidative metabolism of glucose, a fall in acetyl CoA and ATP. Current pharmacological strategies, aimed at increasing cholinergic activity include acetylcholinesterase (AChE) inhibitors, cholinergic agonists, acetylcholine (ACh) releasers and stimulants of nerve growth factors (NGF).

Comparison of the effects of angiotensin II, losartan, and enalapril on baroreflex control of heart rate in conscious rabbits.

We compared the effects of angiotensin II (AII), enalapril, and losartan given by acute intravenous (i.v.) injection, on cardiac baroreflex sensitivity in two groups of conscious normotensive rabbits bred for high gain [> 5 beats/min/mm Hg] (group I) and low gain [< 4 beats/min/mm Hg] (group II) of the mean arterial blood pressure-heart rate (MAP/HR) relationship, respectively.

Improvement of sleep apnoea due to acromegaly during short-term treatment with octreotide.

Two acromegalic patients suffering from severe obstructive sleep apnoea syndrome were treated with the long-acting somatostatin analogue octreotide. Daytime sleepiness and fatigue improved within a few days. Repeat sleep studies performed after octreotide treatment revealed more confluent sleep with a shorter duration of sleep apnoea.

Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors.

The pharmacological and clinical properties of a novel phenyl carbamate acetylcholinesterase (AChE) inhibitor, SDZ ENA 713 are described. In animals and human subjects this compound showed superior chemical stability, oral bioavailability and a longer duration of action than physostigmine. SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects.

Gonadotrophin-releasing hormone agonist and ovarian hyperstimulation syndrome in assisted reproduction.

The available literature concerning the association between gonadotrophin-releasing hormone agonist and ovarian hyperstimulation syndrome has been reviewed and the different patterns by which this agent may contribute to the development of such iatrogenic complication has been elicited, and guidelines have been presented for prevention of this malady. Gonadotrophin-releasing hormone agonist acts directly on human granulosa cells, probably in its own dose-dependent manner. The extent of this action is probably subjected to follicular maturation stage and to the degree of gonadotrophin pre-treatment.

Rabbits with a genetic impairment in baroreceptor reflex sensitivity show abnormal renal haemodynamics and proximal tubular sodium reabsorption in response to a saline infusion.

Objective: To compare renal haemodynamics and proximal tubular sodium reabsorption (PTSR) in response to an acute intravenous saline infusion in rabbits bred for genetic differences in cardiac baroreflex sensitivity (BRS). Rabbits with low BRS increase their blood pressure significantly on a high-salt diet, in association with an initial delay in sodium excretion. It was hypothesized that this could occur through an impaired baroreflex regulation of renal sympathetic nerve activity.

The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in-vitro fertilization patients.

The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer.