Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis.Introduction: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A Ϫ13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. Materials and Methods: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. Results: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by Ϫ7% to Ϫ11% depending on the site measured (p ϭ 0.04). LCT (T/CϪ13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p ϭ 0.001). Milk calcium intake was significantly lower (Ϫ55%, p ϭ 0.004) and aversion to milk consumption was significantly higher (ϩ166%, p ϭ 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. Conclusion:The LCT (T/CϪ13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.

To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE 2 , prostacyclin derivative 6kPGF, a , and thromboxane [Tx] derivative TxB 2 ). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE 2 did not increase in angiotensin rats; however, both 6kPGF, a and TxB 2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 Mg/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF la or TxB 2 . Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG. {Hypertension 1989;14:396-403) A ngiotensin II (Ang II) is intimately involved in / \ the homeostatic regulation of blood pres-.Z \ . sure and body fluids, although the details of its mechanisms of action remain quite controversial. 1In addition to a well-characterized vasoconstrictor action, Ang II has also been proposed to increase peripheral vascular resistance indirectly through peripheral and central mechanisms that lead to an increased activity of the sympathetic nervous system.2 -4 Further, Ang II causes sodium retention both by a direct action on the renal tubule, 5 and through the stimulation of aldosterone release. 5Finally, Ang II administration influences the plasma concentration, renal excretion, and tissue generation of prostaglandins (PGs) that modulate the vasoconstriction.6 However, the relevance of some of these studies to the pathophysiological role of Ang II in hypertension is not clear, as many were conducted during short-term Ang II infusion in animals under anesthesia.To further define mechanisms in the production of Ang II-related hypertension, we infused Ang II into conscious rats over a 14-day period. We measured sympathetic nervous system activity directly with bipolar electrodes implanted on their splanchnic nerves. We determined the excretion of aldosterone and PG (PGE2, 6kPGFi a , and thromboxane [Tx]B 2 ). To further investigate the role of the s...

We studied the effects of serotonin (5-hydroxytryptamine, 5-HT) on glomerular blood flow (GBF) and on renal vessel diameters in the hydronephrotic kidney and in vascular casts of normal kidneys of rats. 5-HT (60 min after local application of 10(-8) mol.liter-1) constricted the arcuate arteries (-10 +/- 2% to -14 +/- 2%, mean +/- SEM), dilated the interlobular arteries (+13 +/- 2%) and afferent arterioles (+17 +/- 3%), and decreased GBF (-44 +/- 5%). In contrast to normal autoregulation, reduction of renal perfusion pressure after local application of 5-HT from 118 +/- 3 mm Hg by 10 and 20 mm Hg reduced GBF by 12 +/- 2% and 23 +/- 3%, respectively. The 5-HT2 antagonist, ritanserin (60 min after local application of 10(-6) mol.liter-1), dilated all preglomerular vessels and increased GBF. In the presence of ritanserin, 5-HT lost nearly all vascular effects. During infusion of 5-HT (5 micrograms.min-1 i.v. for 20 min) vascular reactions were similar to those under local application. After cyclooxygenase inhibition with indomethacin, infusion of 5-HT failed to constrict the arcuate arteries whereas vasodilation of the small preglomerular vessels remained unaffected. Analyzing vascular casts of normal kidneys we observed considerable vascular spasms and an average vasoconstriction of the interlobar arteries of 19 +/- 9% after i.v. infusion of 5-HT. We believe that 5-HT decreases GBF by 5-HT2 receptor-mediated constriction of the large renal vessels which are modulated by the prostaglandin system, whereas 5-HT dilates the small preglomerular vessels, most likely via 5-HT1-like receptors. Furthermore, our data indicate that 5-HT impairs the myogenic component of renal autoregulation in the low pressure range.

Dendritic cells (DC) initiate primary immune reactions and are distributed throughout most tissues. The most potent DC population of the kidney has long been suggested to reside within the glomerular mesangium. Using LEW.1A rats, we enriched and characterized such low-density cells. Mesangial DC generally exhibited round to oval cell bodies and cytoplasmic veils. Phenotypically, these cells were 100% OX-6 þþ , 45% OX-42 þþ , 35% ED1 low , 10% OX-62 low , and negative for ED2 and a-naphtylbutyrate esterase. Introducing a new monoclonal antibody, R3, which stains a subset of splenic DC, we showed strong antigen expression on 60% of mesangial DC. Correlating cell populations were detected immunohistochemically. Functionally, mesangial DC potently stimulated allogeneic mixed leucocyte reactions, but did not phagocytose opsonized Escherichia coli. In addition to their striking phenotypic similarity with autologous splenic DC, mesangial DC exhibited 88% of the allostimulatory activity of splenic DC. Calculation indicated approximately two mesangial DC per glomerulum. We suggest that these cells comprise different maturation-dependent subsets. The OX-62 integrin especially appears to be expressed only on mature mesangial DC, which may correlate to lymphoid veiled cells or interdigitating DC. An employment of mesangial DC in experimental models of acute allograft rejection or glomerulonephritis is discussed. R. Gieseler,

BACKGROUND Brucellosis is the most common zoonosis worldwide and is endemic in the Middle East, Africa, Asia, and Latin America. However, it is uncommon in Central Europe, and periprosthetic infections caused by Brucella are therefore rare. Due to the low prevalence and nonspecific clinical presentation of the disease, accurate diagnosis can be challenging; no gold standard currently exists for treating brucellosis. CASE SUMMARY Here, we present a 68-year-old Afghan woman living in Austria with a periprosthetic knee infection caused by Brucella melitensis. The interval from total knee arthroplasty to septic loosening was five years. A profound medical history and examinations suggested that the patient had been suffering from unrecognized chronic osteoarticular brucellosis prior to total knee arthroplasty. She was successfully treated by two-stage revision surgery and combined antibiotic therapy over three months. CONCLUSION Clinicians should consider brucellosis as a possible cause of chronic arthralgia and periprosthetic infection in patients originating from countries with a high brucellosis burden.