Biomedical subjects

P Shultz

Publications and source records attributed to P Shultz.

12 recordsLinked to original sources

PubMed2000

Prenatally protein-malnourished rats are less sensitive to the amnestic effects of medial septal infusions of chlordiazepoxide.

Evidence is mounting that prenatal protein malnutrition affects the physiological properties of the GABAergic neurotransmitter system in rats. To investigate the functional behavioral consequences of these changes, chlordiazepoxide (CDP, a positive modulator of the GABA(A) receptor) was applied directly to the medial septum and the amnestic response appraised. In adulthood, male offspring of rats provided with a protein-deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy underwent stereotaxic surgery to implant steel cannulae aimed at the medial septum. After recovery, spatial learning performance in the submerged platform version of the Morris water maze task was assessed immediately following a 1 microl infusion of either artificial cerebrospinal fluid (aCSF), or one of three doses of CDP (15, 30 and 60 nmol). Well-nourished control rats demonstrated a robust amnestic response to intraseptal CDP. During task acquisition, well-nourished rats administered each of the doses exhibited significantly longer escape latencies than those given aCSF. On the probe trial (platform removed) a lower proportion of time was spent in the target quadrant (all three doses) at a greater average distance from the former platform location (30 and 60 nmol doses). In contrast, prenatally malnourished rats exhibited a muted sensitivity to CDP, most notable at the 30 nmol dose. These findings provide further support for functional changes within the GABAergic system consequent to malnutrition.

Animals↗

PubMed1998

Efficacy and tolerability of losartan in hypertensive patients with renal impairment. Collaborative Group.

We evaluated the blood pressure-lowering activity, tolerability, and safety of losartan in 112 hypertensive (sitting diastolic blood pressure, 90 to 115 mm Hg) patients with chronic renal insufficiency including mild renal insufficiency (30 to 60 mL/min per 1.73 m2; n=51), moderate to severe renal insufficiency (10 to 29 mL/min per 1.73 m2; n=33), or hemodialysis (n=28). After a 3-week placebo period, once-daily losatan was administered for 12 weeks. The daily dose of 50 mg was increased to 100 mg after 4 weeks in patients whose sitting diastolic blood pressure remained > or = 90 mm Hg or was reduced by < 5 mm Hg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12, the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency; -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg, in moderate to severe renal insufficiency; -17.0/-12.7, -19.1/-14.4, and -22.7/-18.0 mm Hg in hemodialysis. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Losartan was withdrawn in only 6 patients because ofa clinical or laboratory adverse experience. Hyperkalemia (> 6 mEq/L) requiring discontinuation of losartan occurred in only one (group 2) patient. We conclude that once-daily losartan, given as monotherapy at doses of 50 or 100 mg or in combination with other antihypertensive drugs, was effective in reducing blood pressure in hypertensive patients with chronic renal disease and that losartan regimens were well tolerated in all groups, including those on hemodialysis.

Adolescent↗

PubMed1998

Bacteremia and intraoral suture removal: can an antimicrobial rinse help?

Recent studies have shown that bacteremia can result from the removal of intraoral sutures. The authors found that preprocedural use of an antimicrobial oral rinse (0.12 percent chlorhexidine) did not significantly reduce the incidence of bacteremia when compared with no rinse at all. Similarly, a significant relationship between bleeding and bacteremia was not apparent. Most of the positive cultures yielded low colony counts. The results support the rationale for the American Heart Association's 1997 recommendations for use of antibiotic prophylaxis to prevent bacteremia, as well as the importance of good oral hygiene in prevention efforts.

Adolescent↗

PubMed1997

Induction of endothelial cell injury by cigarette smoke.

Cigarette smoke contains different populations of free radicals which may be responsible for endothelial cell (EC) injury of smokers. The purpose of this study was to examine the effects of gas-phase cigarette smoke on EC endothelium-derived relaxing factor (EDRF)/NO-guanylate cyclase (GC)-cGMP pathway and on EC detachment-type injury after incubation with smoke. Furthermore, we examined whether different kind of antioxidants can prevent smoke-caused EC injury. We measured cGMP pathway using direct (sodium nitroprusside, SNP) and indirect (A23187, the calcium ionophore and bradykinin, BK) activators of GC. Directly and indirectly stimulated EC cGMP production dose-dependently decreased and EC detachment increased after incubation with smoke. Externally added thiols (glutathione, GSH; D-Penicillamine, DP; N-acetylcysteine, NAC) protected EC from damage of cGMP production and cell detachment. Other antioxidants (catalase, deferoxamine and superoxide dismutase) were ineffective. These results suggest that the thiol containing GC in EC is destroyed or inactivated or thiol like species responsible for activation of GC is incomplete in EC after incubation with smoke. It is also possible that externally added thiols bind an unknown component of smoke and this way, EC is protected. EC injury may contribute to vascular diseases associated with cigarette smoking.

Animals↗

PubMed1995

Increased nitric oxide synthase activity despite lack of response to endothelium-dependent vasodilators in postischemic acute renal failure in rats.

Lack of response to endothelium-dependent vasodilators generally has been considered to be evidence for decreased nitric oxide synthase (NOS) activity and NO generation after ischemic or hypoxic injury to vital organs including the kidney. In this study, renal blood flow (RBF) responses to endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator prostacyclin, the nonselective NOS inhibitor L-NAME (without and with L-arginine), the inducible NOS inhibitor aminoguanidine, and the NO-donor sodium nitroprusside were examined in 1-wk norepinephrine-induced (NE) and sham-induced acute renal failure (ARF) rats. Compared with sham-ARF, there was no increase in RBF to intrarenal acetylcholine and bradykinin, but a comparable RBF increase to prostacyclin in NE-ARF kidneys. However, there was a significantly greater decline in RBF to intravenous L-NAME in NE- than sham-ARF rats (-65 +/- 8 vs. -37 +/- 5%, P < 0.001) which was completely blocked by prior L-arginine infusion. There was no change in RBF to the inducible NOS specific inhibitor aminoguanidine. Unlike sham-ARF, there was no increase in RBF to intrarenal sodium nitroprusside in NE-ARF. Immunohistochemistry and immunofluorescence detection of constitutive (c) NOS using mouse monoclonal antibody were carried out to positively determine the presence of cNOS in NE-ARF. 90% of renal resistance vessels showed evidence of endothelial cNOS in both sham- and NE-ARF. Taken together, results of these experiments are consistent with the conclusion that NOS/NO activity is, in fact, maximal at baseline in 1-wk NE-ARF and cannot be increased further by exogenous stimuli of NOS activity. The increased NOS is likely of the constitutive form and of endothelial origin. It is suggested that the increased NOS activity is in response to ischemia-induced renal vasoconstrictor activity. Attenuated response to endothelium-dependent vasodilators cannot be interpreted only as evidence for decreased NOS activity.

Acetylcholine↗

PubMed1994

An analysis of spatial navigation in prenatally protein malnourished rats.

Developing rats were either malnourished or adequately nourished during the prenatal period by feeding their dams diets of low (6% casein) or adequate (25% casein) protein content 5 weeks prior to mating and throughout pregnancy. All pups received adequate nutrition from the day of birth onwards. Male offspring were tested in one of two spatial navigation tests in the Morris water tank. In proximal-cue tests (postnatal days 16-20), the position of a platform, which provided a means to escape from swimming, was denoted by an obvious visual cue located directly on the platform. In distal-cue tests (postnatal days 20-27 and adult ages, days 70-71 and days 220-221), the escape platform was submerged below the surface of the water so that the rats were required to use extramaze visual cues to guide them to the platform. Neither proximal-cue nor distal-cue navigation was significantly impaired in the prenatally malnourished rats relative to controls, at any of the ages tested.

Animals↗

PubMed1993

Tertatolol: a beta-blocker with unique effects on human glomerular cell function.

Tertatolol is a beta-blocker with unique renal vasodilatatory effects, mainly at the level of the microcirculation. Since many vasodilatory agents inhibit human mesangial cell (HMC) proliferation, the effects of tertatolol on the incorporation of 3H-thymidine in HMC were studied. Tertatolol plus mitogens (either fetal calf serum, platelet-derived growth factor (PDGF) or bovine thrombin) were incubated with HMC for 28 h, and 3H-thymidine was added during the last 4 h. Trichloroacetic acid-precipitable counts per well were divided by the mean number of cells in representative wells from the same experiment. The effect of tertatolol on angiotensin II (10(-6) mmol/l)-induced HMC contraction was also assessed by measuring the planar surface area of individual cells. In serum-free media, tertatolol did not significantly alter the incorporation of 3H-thymidine after 28 h of incubation in HMC. When tertatolol was added in the presence of 1% serum, 3H-thymidine incorporation was significantly reduced, compared to 1% serum alone. Tertatolol also inhibited 3H incorporation when PDGF and thrombin were used as the stimulus. The increase in cell number normally seen after 7 days in serum was also reduced by tertatolol. Tertatolol inhibited the reduction in planar surface area of HMC induced by angiotensin II. The inhibitory effect of tertatolol on HMC proliferation was also potentiated by ritanserin and MDL 72222, 5HT2 and 5HT3 antagonists, respectively. Conversely, the 5HT1A agonist 8-OH-DPAT did not modify the 3H-thymidine incorporation in HMC in the presence of tertatolol. In conclusion, tertatolol inhibits HMC proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1992

Long-Evans and Sprague-Dawley rats differ in their spatial navigation performance during ontogeny and at maturity.

The Morris maze has become a popular method for the assessment of spatial navigation. However, its use to study the development of spatial abilities has been limited to pigmented rats. Thus, the aim of the present study was to compare albino Sprague-Dawley and pigmented Long-Evans rats using this test during postnatal Days 20 through 27, and Day 90. It was found that Long-Evans rats showed significantly shorter escape latencies and swim distances than the Sprague-Dawley rats on Days 20-25 but not on Days 26-27. However, when tested at Day 90, the Long-Evans rats again showed more rapid location of the escape platform and shorter swim distances than the Sprague-Dawley rats. Probe trial analysis (platform removed) indicated that Long-Evans rats were generally more accurate in their localization of the former platform location than Sprague-Dawley rats. In a second experiment in which 21-day-old rats of both strains were tested in a proximal-cue version of the maze, the question of whether this performance difference might have related to visuo-perceptual differences was considered. Since no dissimilarity in performance was observed, a spatial-learning difference between the two strains would seem best able to explain the preceding data.

Animals↗

PubMed1990

Multifactorial facial pain--differential diagnosis: a case report.

A multidisciplinary algology team was formed to facilitate the diagnosis and treatment of complex head and neck pain disorders. The standard patient evaluation includes a history and physical, surface electromyography, Minnesota Multi-phasic Personality Inventory (MMPI), brief psychiatric interview, dental/occlusal analysis, a postural/musculoskeletal examination; and necessary diagnostic imaging. Clinicians meet in conference after each clinic session. Organic and psychiatric findings are compiled and a differential diagnosis is made. Treatment recommendations are outlined and a review of the evaluation and the therapeutic plan are forwarded to the referring doctor. A typical conference discussion is presented here.

Adult↗

PubMed1990

Interactions of the endothelium and mesangium in glomerular injury.

Glomerular mesangial and endothelial cells have key roles in the regulation of glomerular blood flow, both under normal circumstances and in pathologic states. The anatomic structure of the glomerulus is such that the endothelial and mesangial cells are in close proximity to each other and consequently may communicate through a number of cellular mediators. Vasodilatory substances, such as prostacyclin and endothelium-derived relaxing factor, and vasoconstrictive substances, such as endothelin, are released by endothelial cells and can interact with mesangial cells to affect glomerular blood flow. The ability of plasma macromolecules to enter and circulate through the mesangium may play an important role in the development of glomerular injury. Angiotensin II has been shown to increase the uptake and decrease the rate of disappearance of certain macromolecules in the mesangium; this action is blocked, at least partially, by angiotensin II receptor antagonists and by calcium channel blockers. Experimental studies have suggested that angiotensin converting enzyme inhibitors and calcium channel blockers may prevent or arrest progression of renal injury. Angiotensin converting enzyme inhibitors may ave a beneficial effect by decreasing intraglomerular pressure through inhibition of angiotensin II predominant constriction of the glomerular efferent arteriole and possibly by decreasing mesangial trafficking of macromolecules. Calcium channel blockers may have beneficial effects on intracellular events that occur because of injury of either endothelial or mesangial cells.

Angiotensin II↗

PubMed1989

Regulation of mesangial cell growth by polypeptide mitogens. Inhibitory role of transforming growth factor beta.

Proliferation of mesangial cells is a common histologic abnormality in glomerular diseases. In vivo studies suggest a role for platelets and monocytes-macrophages in mediating glomerular hypercellularity. The authors recently reported that several peptide growth factors stimulate DNA synthesis and growth of human mesangial cells. This article reports that transforming growth factor beta (TGF-beta), a peptide released by inflammatory cells and platelets, inhibits DNA synthesis and growth of human mesangial cells. The stimulatory and inhibitory effects of these mitogens on DNA synthesis and growth was confirmed by autoradiography and cell counting. The inhibitory effect of TGF-beta is not mediated at the receptor level because TGF-beta did not inhibit the binding of epidermal growth factor (EGF) or platelet-derived growth factor (PDGF) to mesangial cells. Because peptide growth factors that stimulate DNA synthesis in mesangial cells induce expression of PDGF mRNAs, the effect of TGF-beta on PDGF mRNAs expression induced by peptide growth factors was studied. TGF-beta did not lower the increased levels of PDGF mRNAs caused by EGF or PDGF. These data show that TGF-beta is a potent inhibitor of DNA synthesis and growth of mesangial cells. The mechanism of the inhibitory effect of TGF-beta remains to be determined.

Cell Division↗

PubMed1988

Mechanisms of hypertensive glomerular injury.

Systemic hypertension complicates the course of most patients with chronic renal failure and accelerates the progression of experimental and clinical glomerular disease. Based on recent experimental studies, it is suggested that at similar levels of systemic hypertension, glomerular injury only develops when pre-glomerular resistances are ineffective, thus allowing the development of glomerular hypertension. The mechanisms by which the hemodynamic stress of elevated intracapillary flows and pressures leads to progressive glomerular damage, particularly to the development of focal glomerulosclerosis is currently unknown. Endothelial cell injury, increased mesangial traffic or trapping of macromolecules and epithelial cell injury, or a combination, appear to occur early, followed by in situ inflammatory and microthrombotic mechanisms. This may explain why various therapeutic approaches, whether dietary or pharmacologic, can have salutory effects despite their diverse mechanisms of action.

Animals↗