ABSTRACT
Thyrotoxic periodic paralysis (TPP) is a rare muscular disorder, characterized by muscle weakness and hypokalemia triggered by thyrotoxicosis. In Asian populations, 2% of patients with thyrotoxicosis are affected, compared to only 0.1-0.2% of non-Asians. The vast majority of patients are male. Muscle weakness ranges in severity from very mild to life-threatening, due to respiratory compromise. We present a case of a previously healthy 39-year-old Hispanic male who presented with sudden quadriparesis and quickly recovered after being treated for hypokalemia and thyrotoxicosis. TPP, although unusual, is important to recognize as it is a potentially fatal condition that requires close monitoring and is readily reversible with appropriate therapy. Any cause of thyroid hormone excess can cause TPP, with Graves' disease being the most common etiology. Acute treatment includes potassium repletion, while long-term management focuses on determining and treating the cause of thyrotoxicosis, since maintaining a euthyroid state will prevent further episodes of TPP.
ABSTRACT
Vitamin D is a steroid hormone with canonical roles in calcium metabolism and bone modeling. However, in recent years there has been a growing body of literature presenting associations between vitamin D levels and a variety of disease processes, including metabolic disorders such as diabetes and prediabetes and autoimmune conditions such as thyroid disease. This review focuses on the potential role of vitamin D in both male and female reproductive function. The vitamin D receptor (VDR) is expressed throughout central and peripheral organs of reproduction. VDR is often co-localized with its metabolizing enzymes, suggesting the importance of tissue specific modulation of active vitamin D levels. Both animal and human studies in males links vitamin D deficiency with hypogonadism and decreased fertility. In females, there is evidence for its role in polycystic ovary syndrome (PCOS), endometriosis, leiomyomas, in-vitro fertilization, and pregnancy outcomes. Studies evaluating the effects of replacing vitamin D have shown variable results. There remains some concern that the effects of vitamin D on reproduction are not direct, but rather secondary to the accompanying hypocalcemia or estrogen dysregulation.
Subject(s)
Reproduction , Vitamin D/metabolism , Animals , Endometriosis/etiology , Endometriosis/genetics , Endometriosis/metabolism , Female , Fertilization in Vitro , Humans , Infertility/etiology , Infertility/genetics , Infertility/metabolism , Male , Polycystic Ovary Syndrome/etiology , Polycystic Ovary Syndrome/genetics , Polycystic Ovary Syndrome/metabolism , Pregnancy , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Vitamin D/genetics , Vitamin D Deficiency/complications , Vitamin D Deficiency/genetics , Vitamin D Deficiency/metabolismABSTRACT
A QSAR based predictive model of hERG activity in terms of 'global descriptors' has been developed and evaluated. The QSAR was developed by training 77 compounds covering a wide range of activities and was validated based on an external 'test set' of 80 compounds using neural network method. Statistical parameters and examination of enrichment factor indicated the effectiveness of the present model. Randomization test demonstrated the robustness of the model and cross-validation test further validated the QSAR. Domain of applicability test indicated to the high degree of reliability of the predicted results. Satisfactory performance in classifying compounds into 'active' and 'inactive' groups was also obtained. The cases where the QSAR failed, the possible sources of errors have been discussed.
Subject(s)
Computer Simulation , Ether-A-Go-Go Potassium Channels/chemistry , Organic Chemicals/chemistry , Quantitative Structure-Activity Relationship , Ether-A-Go-Go Potassium Channels/antagonists & inhibitors , Ether-A-Go-Go Potassium Channels/metabolism , Humans , Molecular Structure , Organic Chemicals/pharmacologyABSTRACT
Simultaneous oscillations of 1318.8nm, 1320.0nm, 1332.6nm, 1335.0nm, 1338.2nm and 1339.0nm in a side, pulsed-diode-laser-array pumped Nd:YAG laser is realized for both free running and Q-switched operation. An average power of 1.1W is obtained for an absorbed pump power of 7.1W with an effective optical slope efficiency of 33%. The difference frequency interactions among these wavelengths may be used to generate radiation in the range 0.13-3.43THz. With the two most intense lines at 1318.8nm and 1338.2nm, it is possible to generate coherent radiation at 3.3THz with numerically estimated peak power of 0.21W in a 1.5mm thick GaSe crystal.
ABSTRACT
BACKGROUND: It has been suggested that peroxisome proliferator-activated receptor (PPAR)-gamma ligands reduce the development of atherosclerosis and myocardial ischemia-reperfusion injury; both of these phenomena are associated with platelet activation. We postulated that PPAR-gamma activation would inhibit platelet activation and intra-arterial thrombus formation. METHODS AND RESULTS: Sprague-Dawley rats were fed chow mixed with pioglitazone (1 or 10 mg/kg/day) for 7 to 10 days. A filter soaked in 30% FeCl(3) was applied around the abdominal aorta to study the patterns of arterial thrombogenesis. The aortic blood flow was continuously monitored using an ultrasonic Doppler flow probe. ADP and arachidonic acid-induced platelet aggregation and the expression of constitutive nitric oxide synthase (cNOS) and thrombomodulin in aorta were measured. Pioglitazone feeding delayed the time to occlusive thrombus formation by 40% (P<0.01 vs. control, n=9) without affecting the weight of the thrombus. ADP- as well as arachidonic acid-induced platelet aggregation was also inhibited by pioglitazone feeding (P<0.01 vs. control, n=9). Pioglitazone feeding also upregulated the aortic expression of cNOS and thrombomodulin; both are considered important factors in platelet aggregation and thrombus formation in vivo. The effect of a high dose (10 mg/kg/day) of pioglitazone was not more potent than that of a low dose (1 mg/kg/day). CONCLUSION: These results indicate that pioglitazone administration decreases platelet aggregation and delays intra-arterial thrombus formation in rats, at least partially, by an increase in the expression of cNOS and thrombomodulin.