Distal Convoluted Tubule

The distal convoluted tubule is the nephron segment that lies immediately downstream of the macula densa. Although short in length, the distal convoluted tubule plays a critical role in sodium, potassium, and divalent cation homeostasis. Recent genetic and physiologic studies have greatly expanded our understanding of how the distal convoluted tubule regulates these processes at the molecular level. This article provides an update on the distal convoluted tubule, highlighting concepts and pathophysiology relevant to clinical practice.     

Mindfulness (Vipassana) meditation: Effects on P3b event-related potential and heart rate variability

The concept of mindfulness is based on Vipassana, a Buddhist meditation technique. The present study examines the physiological indices of attention and autonomic regulation in experienced Vipassana meditators to test the claim that mindfulness is an effective therapeutic tool due to its effects on increasing awareness of present experience and emotional self-regulation. Ten male experienced Vipassana meditators underwent two assessment sessions, one where they practiced Vipassana meditation and another where they rested with no meditation (random thinking). Each meditation/no-meditation session lasted 30 min and was preceded and followed by an auditory oddball task with two tones (standard and target). Event-related potentials to the tones were recorded at the Fz, Cz, and Pz locations. Heart rate variability, derived from an EKG, was recorded continuously during the meditation/no-meditation sessions and during a 5-minute baseline before the task. The Vipassana experts showed greater P3b amplitudes to the target tone after meditation than they did both before meditation and after the no-meditation session. They also showed a larger LF/HF ratio increase during specific Vipassana meditation. These results suggest that expert Vipassana meditators showed increased attentional engagement after meditation and increased autonomic regulation during meditation supporting, at least partially, the two claims concerning the clinical effectiveness of mindfulness.     

Safety and efficacy of radiofrequency energy catheter ablation of atrial fibrillation in patients with pacemakers and implantable cardiac defibrillators

BACKGROUND: Catheter ablation has significantly transformed the clinical management of atrial fibrillation (AF). The safety and efficacy of this procedure are not well understood in patients with pacemakers and defibrillators. OBJECTIVES: The purpose of this study was to study the impact of radiofrequency catheter ablation of AF in patients with pacemakers and implantable cardiac defibrillators. METHODS: We studied 86 patients with pacemakers and defibrillators (group I) and a similar number of age- and gender-matched controls (group II) who underwent AF ablation between 1999 and 2004. Clinical and procedural variables were compared between the two groups. In group I, various generator and lead parameters were compared before and after the procedure. Resurgence of clinical AF after 2 months was considered recurrence. RESULTS: Both groups were similar with regard to age, gender, body mass index, and type of AF. Group I had a higher incidence of diabetes (17% vs 6%, P = .03), coronary artery disease (25% vs 13%, P = .05), less prolonged AF (31 +/- 21 vs 45 +/- 30 months, P <.001), lower left ventricular ejection fraction (49 +/- 13% vs 52 +/- 9%, P = .03), and left ventricular end-diastolic dimensions (4.97 +/- 0.81 vs 4.72 +/- 0.67, P = .03). No changes in the sensing and pacing thresholds, impedance of atrial and ventricular leads, or defibrillator coil impedance after AF ablation were observed in group I. Atrial lead dislodgment was seen in two patients. Transient abnormal but "expected" pulse generator behavior was seen in 25% of patients without permanent malfunction. Stroke (1% vs 1%, P = 1.000), pulmonary vein stenosis (2% vs 1%, P = .77), and AF recurrence rates at 12 months were similar between groups I and II, respectively (19% vs 21%, P = .73). CONCLUSION: AF ablation is safe and efficacious in patients with pacemakers and defibrillators.     

A case of metastatic rectal adenocarcinoma diagnosed by thyroid cytology

Fine‐needle aspiration (FNA) cytology of the thyroid gland has been widely used for the evaluation of thyroid nodules. Most of the nodules are primary thyroid lesions. However, up to 4% of thyroid FNA may harbor a metastatic neoplasm. The metastases are most commonly from lung, kidney, breast, and skin. Metastatic colorectal cancers are also seen in thyroid but less common. Here we report the cytologic features, differential diagnosis and clinical implications of a metastatic rectal adenocarcinoma to the thyroid gland diagnosed by FNA.     

Lipid peroxidation in different tissues: effect of high cholesterol and fish oil in the diet

Malonyldialdehyde was measured in erythrocytes, aorta and spleen on feeding mice with high cholesterol diet in presence and absence of fish oil. Mice were grouped as: Group I: Control laboratory diet Group II: 0.16% cholesterol (sunflower oil) Group III: 1.16% cholesterol (sunflower oil) Group IV: 1.16% cholesterol (fish oil) After 7 weeks on their respective diets, erythrocytic, and splenic MDA levels were significantly higher in group III compared to controls. Also, MDA levels in aorta and spleen showed a significant increase in group IV males compared to group III males. However in group IV the erythrocyte MDA levels were almost equal to that in controls. This suggests that high cholesterol diet increases lipid peroxidation in erythrocytes, spleen and aorta. Addition of fish oil in the diet further increases lipid peroxidation in aorta and spleen, but not in the erythrocytes.     

Pharmacology and toxicology of cholinesterase inhibitors: uses and misuses of a common mechanism of action

Cholinesterase inhibitors have been used in the treatment of human diseases, the control of insect pests, and more notoriously as chemical warfare agents and weapons of terrorism. Most uses of cholinesterase inhibitors are based on a common mechanism of action initiated by inhibition of acetylcholinesterase (AChE). Extensive inhibition of this enzyme leads to accumulation of the neurotransmitter acetylcholine and enhanced stimulation of postsynaptic cholinergic receptors. This action is beneficial in cases where a reduction in cholinergic transmission contributes to clinical symptoms, e.g., low muscle tone in the autoimmune disorder myasthenia gravis due to loss of nicotinic receptors. Under normal conditions, however, extensive inhibition of AChE leads to excess synaptic acetylcholine levels, over-stimulation of cholinergic receptors, alteration of postsynaptic cell function and consequent signs of cholinergic toxicity. This biochemical cascade forms the basis for the use of anticholinesterase insecticides in pest control as well as for nerve agents in chemical warfare. Paradoxically, the short-acting cholinesterase inhibitor pyridostigmine, an important therapeutic agent in the treatment of myasthenia gravis, was used during the Persian Gulf War to prevent the long-term clinical consequences of possible organophosphate nerve agent exposure. As shown in the attacks in Matsumoto and Tokyo, these same nerve agents can be effectively used to inflict urban terror. Cholinesterase inhibitors thus share a common mechanism of pharmacological or toxicological action, ultimately modifying cholinergic signaling through disruption of acetylcholine degradation. While the use of cholinesterase inhibitors relies on their interaction with AChE, a variety of reports indicate that a number of cholinesterase inhibitors have additional sites of action that may have pharmacologic or toxicologic relevance. A variety of esterase and non-esterase enzymes, neurotransmitter receptors and elements of cell signaling pathways are targeted by some anticholinesterases. In some cases, these actions may occur at concentrations/dosages below those affecting cholinergic transmission. Studies of interactive toxicity of binary mixtures of common organophosphorus insecticides indicate that non-cholinesterase targets may be important in cumulative toxicity. Exposure to multiple anticholinesterases having selective effects on other macromolecules could confound the assumption of additivity in cumulative risk assessment. Knowledge of such selective additional targets may aid, however, in the optimization of strategies for poisoning therapy and in the further elucidation of mechanisms of toxicity for this class of compounds.     

Atherogenic effect of interleukin-2 and antiatherogenic effect of interleukin-2 antibody in apo-E-deficient mice

Growing evidence suggests that atherosclerosis is an immune-mediated inflammatory process and that cytokines participate as mediators in this process. Of the cytokines, interleukins, which are released from both immune and nonimmune cells of vascular wall, are found to have multiple effects. Interleukin-2 (IL-2), a cytokine produced by activated T-lymphocytes, has been found to further activate the T cells and may potentially enhance atherogenesis. Apo-E-deficient mice fed with atherogenic diet were injected intraperitoneally twice a week with placebo, IL-2, or anti-IL-2 antibody for a period of 6 weeks. Group 1 (n = 6) was injected with bovine serum albumin (BSA) in phosphate-buffered saline (PBS) and served as controls. Group 2 (n=6) was injected with 2 x 10(4) units of recombinant murine IL-2 (rmIL-2) per dose reconstituted with BSA in PBS. Group 3 (n=6) was injected with 5 microg of anti-IL-2 per dose reconstituted with BSA in PBS. Aortic sections were analyzed and atherosclerotic burden was quantified. Compared to controls, injection of IL-2 increased measures of atherosclerosis such as the average lesion score (10.7 +/-0.5 vs 9.3 +/-1.1, p=0.04) and the lesion size as a fraction of aortic area (0.51 +/-0.03 vs 0.41 +/-0.05, p=0.01). Injection of anti-IL-2 had a profound antiatherogenic effect. It significantly reduced the average number of lesions per cross section (2.6 +/-0.6 vs 4.3 +/-0.6, p=0.03), the average lesion score (4.6 +/-1.9 vs 9.3 +/-1.1, p=0.02), the lesion area/circumference (0.35 +/-0.08 vs 0.62 +/-0.10, p=0.007), and the lesion size/aortic area (0.23 +/-0.07 vs 0.41 +/-0.05, p=0.03). These results indicate that IL-2 is an atherogenic cytokine in apo-E-deficient mice and anti-IL-2 is protective against atherosclerosis. This may have important clinical implications in modifying the atherosclerotic process.     

Age-related effects of chlorpyrifos and parathion on acetylcholine synthesis in rat striatum

We compared the in vivo effects of two organophosphorus (OP) insecticides, chlorpyrifos (CPF) and parathion (PS) on acetylcholine (ACh) synthesis in neonatal, juvenile and adult rats. Basal levels of ACh synthesis were highest in adult rats, intermediate in juveniles and lowest in neonates. Following high (maximum tolerated dosage) subcutaneous exposure to either insecticide, relatively similar degrees of cholinesterase inhibition were noted, but the time to peak reduction varied among the age groups. CPF had no effect on ACh synthesis in neonates, increased synthesis in juveniles and decreased synthesis in adults, but only in the low dose group. PS had more consistent effects on ACh synthesis, decreasing transmitter synthesis in neonates (24 h after dosing) but increasing synthesis in juveniles and adults at both 4 and 24 h after exposure. Selective changes in neurotransmitter synthesis may contribute to differential age-related toxicity of these agents.