The effect of serotonin and serotonin receptor antagonists on motion sickness in Suncus murinus

In the present study, we investigated the effect of 5-hydroxytryptamine (5-HT) and 5-HT receptor agonists and antagonists on motion sickness in Suncus murinus, and the possibility that the emetic stimulus of 5-HT can alter the sensitivity of the animals to the different emetic stimulus of motion sickness. 5-HT (1.0, 2.0, 4.0 and 8.0 mg/kg ip) induced emesis and that was antagonised by methysergide (1.0 mg/kg ip), the 5-HT(4) receptor antagonist sulphamate[1-[2-[(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate (GR125487D; 1.0 mg/kg ip) and granisetron (0.5 mg/kg ip). Pretreatment with 5-HT caused a dose-related attenuation of the emetic response induced by a subsequent motion stimulus, which was not significantly modified by methysergide, granisetron or GR125487D pretreatment. (+)-1-(2,5-Dimethoxy-4-iodophenyl)-2-amino-propane (DOI; 0.5 and 1.0 mg/kg ip), 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT; 0.1 mg/kg ip) but not methysergide, GR125487D or granisetron, attenuated motion-induced emesis, and that was not affected by pretreatment with ketanserin (2.0 mg/kg, ip) or N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydrocholoride (WAY-100635; 1.0 mg/kg ip), respectively. Indeed, ketanserin alone (0.1, 0.3, 1.0 and 2.0 mg/kg ip) attenuated motion sickness. These data indicate that 5-HT(1/2), 5-HT(3) and 5-HT(4) receptors are involved in the induction of 5-HT-induced emesis. However, agonist action at the 5-HT(1A/7) and 5-HT(2) receptors, and antagonist action at the 5-HT(2A) receptors can attenuate motion sickness in S. murinus.     

Role of inhaled nitric oxide as a selective pulmonary vasodilator in pediatric cardiac surgical practice

Our aim was to assess the role of inhaled nitric oxide (NO) therapy in post operative cases of congenital heart defects who developed pulmonary arterial hypertensive (PAH) crisis and had no response with conventional management. From February '95 to January '97, inhaled NO therapy was used in 21 children. Age ranged from 2 months to 9 years (mean 5.6 years) and duration of therapy ranged from 1 to 13 days. Of 21 patients, 17 responded well with 5–20 ppm while 4 did not. The preoperative mean pulmonary systolic pressure was 88 mm Hg against mean systemic pressure of 96 mm Hg. Post operatively, their PA pressure reduced to 62 mm Hg, with systemic pressure of 98 mm Hg. After using inhaled NO, PA pressure dropped to 24 mm Hg (mean systolic) (p<0.007), after excluding the non responders. Of 4 non responders, two died due to irreversible pulmonary vascular disease and remaining two died due to residual defects. The study shows that inhaled NO is a selective pulmonary vasodilator, which is useful in postoperative PAH crisis and also reduces the transpulmonary gradient in single ventricle repair cases. It is safe and effective for prolonged use. It is very useful in Indian perspective, when more number of cases with congenital heart defects (CHD) alongwith severe PAH are encountered routinely.     

Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2

Modification of mammalian DNA by the methylation of cytosinein CpG dinucleotides is a complex phenomenon involved in a numberof cellular and developmental processes. In a particular, thecharacteristic hypermutability of CpGs may be a major contributorof point mutations leading to human genetic disease. We havehypothesized that DNA methylation contributes to mutations inthe gene causing neurofibromatosis type 1 (NF1), one of themost common genetic disorders in humans and a disease whereup to half of all cases are the result of sporadic germlinemutations, usually in the paternally-derived allele. We haveused two experimental approaches to analyze patterns of DNAmethylation at CpG dinucleotides in the NF1 gene region. Southernanalyses using isoschizomeric restriction pairs have revealedDNA methylation in areas flanking the NF1 gene region, whilePCR-methylation assays have shown that methylation occurs bothon genomic sequences flanking the NF1 gene and within the codingregion of the gene itself. We suggest that methylated CpG dinucleotideswithin and around the highly mutable NF1 gene serve as a reservoirwithin which C-T transitions contribute to the high frequencyof spontaneous germline mutations associated with the disease.     

The impact of work-related risk on nurses during the SARS outbreak in Hong Kong

Severe acute respiratory syndrome (SARS) is a highly infectious disease, with high potential for transmission to close contacts, particularly among healthcare workers. This is the first systematic study investigating hospital nurses' physical and psychological health status and the kinds of healthcare used-stratified by the level of contact with SARS patients-during the 2003 outbreak in Hong Kong. Nurses in moderate-risk areas appeared to have more stress symptoms than those working in high-risk areas. It is essential to design hospital support systems and occupational health policy to promote the psychological well-being of nurses during future outbreaks of emerging infections.     

(-)-Epigallocatechin gallate as an intervention for the acute treatment of cerebral ischemia

This study examined the neuroprotective effects and possible hepatotoxicity of (-)-epigallocatechin gallate (EGCG) in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats (265-295 g) were treated with either 50 mg kg(-1) of EGCG or saline, i.p., immediately post-ischemia and every day thereafter, in a middle cerebral artery occlusion model of stroke. Sacrifice occurred 72 h post-ischemia and 2,3,5-triphenyltetrazolium chloride staining was used to quantify neuronal infarction. Hepatotoxicity was determined by taking blood samples for plasma alanine aminotransferase (ALT) activity. Spleen, kidney, liver and testes wet weights were also recorded. Total infarct volume was significantly (P<0.05) reduced in the EGCG-treated group as compared to controls. Analysis of the mean infarct area showed a significant (P<0.05) decrease in slices 6 and 7 in the EGCG-treated group. No significant differences were found in organ weights or ALT levels between treatment groups. Our findings, in part, validate and extend previous observations illustrating that 50 mg kg(-1), i.p. EGCG is non-toxic and neuroprotective. However, we also found that EGCG treatment appreciably increased (>50%) the number of animals that developed an intracerebral hemorrhage. We therefore conclude that 50 mg kg(-1) EGCG is not a viable intervention for the acute treatment of cerebral ischemia, as it is likely to increase the risk of intracerebral hemorrhaging.