Use of tolazoline enahanced superior mesenteric arteriography to improve opacification of a cecal vascular ectasia: a case report

The use of vasodilators to enhance venous opacification during superior mesenteric arteriography is well established. This is a report on the use of intra-arterial tolazoline hydrochloride during angiography to improve opacification of a cecal vascular ectasia which was poorly demonstrated on an arteriogram performed without tolazoline.     

Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons

The heart slows during expiration and heart rate increases during inspiration. This cardiorespiratory interaction is thought to occur by increased inhibitory synaptic events to cardiac vagal neurons during inspiration. Since cholinergic receptors have been suggested to be involved in this cardiorespiratory interaction, we tested whether endogenous cholinergic activity modulates GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus, whether nicotine can mimic this facilitation, and we examined the nicotinic receptors involved. Cardiac vagal neurons in the rat were labeled with a retrograde fluorescent tracer and studied in an in vitro slice using patch-clamp techniques. Application of neostigmine (10 microM), an acetylcholinerase inhibitor, significantly increased the frequency of both GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) in cardiac vagal neurons. Exogenous application of nicotine increased the frequency and amplitude of both GABAergic and glycinergic IPSCs. The nicotinic facilitation of both GABAergic and glycinergic IPSCs were insensitive to 100 nM alpha-bungarotoxin but were abolished by dihydro-beta-erythrodine (DHbetaE) at a concentration (3 microM) specific for alpha4beta2 nicotinic receptors. In the presence of TTX, nicotine increased the frequency of GABAergic and glycinergic miniature synaptic events, which were also abolished by DHbetaE (3 microM). This work demonstrates that there is endogenous cholinergic facilitation of GABAergic and glycinergic synaptic inputs to cardiac vagal neurons, and activation of alpha4beta2 nicotinic receptors at presynaptic terminals facilitates GABAergic and glycinergic neurotransmission to cardiac vagal neurons. Nicotinic facilitation of inhibitory neurotransmission to premotor cardiac parasympathetic neurons may be involved in generating respiratory sinus arrhythmia.     

Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus

Activation of opioid receptors in the CNS evokes a dramatic decrease in heart rate which is mediated by increases in inhibitory parasympathetic activity to the heart. Injection of opiates into the nucleus ambiguus, where premotor cardiac parasympathetic nucleus ambiguus neurons are located elicits an increase in parasympathetic cardiac activity and bradycardia. However, the mechanisms responsible for altering the activity of premotor cardiac parasympathetic nucleus ambiguus neurons is unknown. This study examined at the electron microscopic level whether premotor cardiac parasympathetic nucleus ambiguus neurons possess postsynaptic opioid receptors and whether mu-opioid receptor agonists alter voltage-gated calcium currents in these neurons. Premotor cardiac parasympathetic nucleus ambiguus neurons were identified in the rat using retrograde fluorescent tracers. One series of experiments utilized dual-labeling immunocytochemical methods combined with electron microscopic analysis to determine if premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. In a second series of experiments whole cell patch clamp methodologies were used to determine whether activation of postsynaptic opioid receptors altered voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons in brainstem slices. The perikarya and 78% of the dendrites of premotor cardiac parasympathetic nucleus ambiguus neurons contain mu-opioid receptors. Voltage-gated calcium currents in premotor cardiac parasympathetic nucleus ambiguus neurons were comprised nearly entirely of omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents. Activation of mu-opioid receptors inhibited these voltage-gated calcium currents and this inhibition was blocked by pretreatment with pertusis toxin. The mu-opioid receptor agonist endomorphin-1, but not the mu-opioid receptor agonist endomorphin-2, inhibited the calcium currents. In summary, mu-opioid receptors are located postsynaptically on premotor cardiac parasympathetic nucleus ambiguus neurons. The mu-opioid receptor agonist endomorphin1 inhibited the omega-agatoxin-sensitive P/Q-type voltage-gated calcium currents in premotor cardiac vagal nucleus ambiguus neurons. This inhibition is mediated via a G-protein mediated pathway which was blocked by pretreatment with pertusis toxin. It is possible that the inhibition of calcium currents may act to indirectly facilitate the activity of premotor cardiac parasympathetic nucleus ambiguus neurons by disinhibition, such as by a reduction in inhibitory calcium activated potassium currents.     

Carrier Screening for β Thalassemia in Pregnant Indian Women: Experience at a Single Center in Madhya Pradesh

To study the prevalence of β thalassemia trait in pregnancy in urban population screening for β thalassemia in pregnant women at a single center in Indore (MP) has been conducted for a period of 2 year. Blood samples were tested for complete blood count and hemoglobin electrophoresis. During the 2 year period a total of 1,006 women were screened; 28 women who carried abnormal pattern were detected. The mean gestational age for screening was 13 ± 4 weeks. The prevalence of carriers was 2.78 %. As much as 99 % of pregnant women undergoing screening were willing for prenatal diagnosis if required. The economic burden to the society for treating thalassemic patients is huge. The institution of prevention programs like carrier screening has proven costeffective in populations with a high frequency of carriers. Screening of pregnant women early in pregnancy followed by prenatal diagnosis is acceptable and effective strategy for control of thalassemia in developing countries like India.     

Prior cadmium exposure improves glucoregulation in diabetic rats but exacerbates effects on metabolic dysregulation, oxidative stress, and hepatic and renal toxicity

The present study was taken up to assess the role of subchronic exposure to an environmentally relevant dosage of cadmium in type l diabetes. Female rats of the Wistar strain were treated with cadmium (5.12?mg/kg body weight) for 45 days. On day 46, rats were made diabetic by alloxan. After 7 days, diabetes (i.e., animals with serum glucose greater than 300?mg/dL) in the alloxanized animals was confirmed and further experiments were conducted for 15 days. Cadmium pretreatment showed disturbed glucose homeostasis with attendant changes in carbohydrate metabolism, coupled with decrease in food and water intake. Disturbance in carbohydrate metabolism was indicated by altered tissue metabolite load, as marked by a decrease in protein and glycogen contents and increased cholesterol store. Poor glucose clearance subsequent to a glucose challenge under the glucose tolerance test was observed in these animals (0.48/min in control vs. 0.13/min in Cd animals). There was a significantly lower glucose elevation rate in the insulin response test subsequent to an insulin-induced decrease in glucose level in Cd-exposed animals. Elevated oxidative stress was marked by increased lipid peroxidation, decreased antioxidant (both nonenzymatic and enzymatic) levels, and serum markers of hepatic and renal damage. Decreased corticosterone levels, together with increased E2 and reduced P4 levels, were some of the hallmark changes in the serum hormone profile of Cd-exposed animals. Overall, the present results are novel and interesting to open more investigations on animal models of type 1 diabetes with a history of previous Cd exposure.     

Erratum to: A Combination of Melatonin and Alpha Lipoic Acid has Greater Cardioprotective Effect than Either of them Singly Against Cadmium-Induced Oxidative Damage

Present study evaluates cardioprotective role of melatonin (Mel), alpha lipoic acid (ALA), a combination of melatonin and alpha lipoic acid (Mel + ALA) against cadmium (Cd)-induced oxidative damage. Female albino rats were subjected to 15-day exposure to Cd (5.12 mg/kg bw) alone or treated with ML (10 mg/kg bw) + ALA (25 mg/kg bw) simultaneously. Plasma markers of cardiac damage, cardiac free radical generation, lipid peroxidation, endogenous antioxidant status, cadmium load, metallothionein induction, and histopathology were evaluated in various experimental groups. Combination of Mel + ALA significantly prevented leakage of marker enzymes of cardiac damage, changes in cardiac free radical generation, endogenous antioxidants, antioxidant status, structural alterations and augmented the degree of metallothionein (MT) induction. The results demonstrate that ML + ALA co-administration effectively protected against Cd-induced cardiac oxidative damage.