<i>Background:</i> Spontaneous peritonitis is a rather rare event, even in peritoneal dialysis (PD). As defensins are natural antimicrobial peptides, we hypothesized that adipocytes as the major constituents of the omentum could play an important role in protecting against infection by generating defensin (DEFA1–3). <i>Methods:</i> We isolated adipocytes from the omentum majus and conducted qualitative and quantitative RT-PCR and immunohistochemical analyses. <i>Results:</i> For the first time described, we were able to detect DEFA1–3 mRNA in highly purified isolated omental adipocytes. The expression of DEFA1–3 in adipocytes was confirmed on the protein level by immunohistochemistry. <i>Conclusion:</i> Our report of DEFA1–3 expression by human omental adipocytes adds to the role of adipocytes in the primary defense against bacterial infection. This may include PD, where the presence of the catheter as a foreign body and the nonphysiological dialysis solution may require constant defense measures to prevent peritonitis, a hypothesis that will require further testing.
There is considerable evidence from clinical and experimental studies that blood pressure is lowered by converting enzyme inhibitors (CEIs) irrespective of whether the plasma renin-angiotensin system (RAS) is stimulated. New insights into the molecular biology of the RAS--in particular, the gene expression of renin and angiotensinogen in various tissues--support the view that the antihypertensive properties of CEIs may be mediated, at least in part, by interaction with tissue RAS. To investigate this possibility further, stroke-prone spontaneously hypertensive male rats (SHRSP) were treated orally for 28 days with different CEIs or a peripheral vasodilator to study the effects of the various drug treatments on the gene expression of the RAS in selected tissues. Different effects of different CEIs on tissue gene expression suggest localized action and some degree of organ specificity of the drugs. The experiments involved: (1) untreated controls; and rats treated with either (2) 50 mg/kg of captopril; (3) 10 mg/kg of lisinopril; (4) 10 mg/kg of cilazapril; (5) or 30 mg/kg of the vasodilator hydralazine with 10 rats/group. All of the study drugs reduced systolic blood pressure to normotension. Cardiac hypertrophy and the heart:body weight ratio were significantly decreased only in the CEI-treated animals, and kidney renin mRNA was increased by the CEIs whereas hydralazine had no effect on heart weight or kidney renin mRNA. Plasma renin activity increased in parallel with kidney renin mRNA levels. Liquid hybridization and Northern blotting assays revealed drug-specific regulation of the angiotensinogen mRNA level in the adrenal gland, with cilazapril producing the most marked stimulation of adrenal angiotensinogen gene expression. Both lisinopril and cilazapril suppressed hypothalamic angiotensinogen mRNA. There were no significant changes in angiotensinogen gene expression observed in the kidney or liver with any of the CEIs. In conclusion, these data show that CEIs interact differentially and drug-specifically with tissue RAS, and have class-specific effects on cardiac hypertrophy.
Hypothyroidism with thyroglobulin antibodies during corticoid replacement in a 54-year-old man with isolated ACTH deficiency. HISTORY AND ADMISSION FINDINGS: A 54-year-old previously healthy man was admitted because of fatigue, tiredness, diarrhoea and weight loss for the last 3 years. Physical examination revealed dry but normally pigmented skin and markedly reduced Achilles reflex bilaterally. INVESTIGATIONS: Erythrocyte sedimentation rate was slightly elevated at 32 mm/h, C-reactive protein was normal. Both haemoglobin (12.4 mg/dl) and the corpuscular indices were normal, as were serum electrolytes, and sodium bicarbonate. But basal levels of thyroid stimulating hormone (TSH, 8.5 mU/ml) was markedly elevated, while free peripheral triiodothyronine (3.2pg/ml) was normal and free thyroxine (fT4) at 0.7 ng/d was slightly reduced. Thyroid ultrasound was normal. Test for antinuclear antibodies was slightly positive, but double-strand DNA was not demonstrated. Antithyroglobulin antibodies were slightly raised to 1012 IU/ml (normal <350). The basic level of ACTH was repeatedly below detection, as were plasma cortisol and cortisol excretion in 24-hour urine. Nuclear magnetic imaging was normal. Failure to stimulate corticol synthesis in the short ACTH test and by CRH indicated an isolated ACTH deficiency at the level of the anterior pituitary, while other hypophyseal functions were unaffected. TREATMENT AND COURSE: The patient"s condition rapidly improved on replacement with hydrocortisone, 30 mg/d, and thyroxine, 100 mg/d. No thyroglobulin antibodies or antinuclear antibodies were demonstrable after 6 months. Thyroxine was discontinued after 15 months. Frequent monitoring of thyroid function over the next 2 years always indicated a euthyroid state. CONCLUSION: Subnormal concentration of peripheral thyroid hormone combined with elevated TSH levels can, in the presence of hypercorticolism, be due to reversible abnormal thyroid function.
When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of whether or not the plasma RAS was stimulated. Several other effects had to be considered. It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered. The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.
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