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Biomedical subjects

V Herrmann

Publications and source records attributed to V Herrmann.

At least 19 recordsLinked to original sources
PubMed2006

The impact of pregnancy and childbirth in the urethra of female rats.

The aim of this study was to evaluate the modifications in the amount of collagen, muscular, and elastic fibers in the mid-urethra of adult female rats during the pregnancy and after the natural childbirth, cesarean, and after simulated trauma of childbirth. The authors evaluated the histomorphometric aspects (collagen, muscular, and elastic fibers) in the mid-urethra of 70 animals distributed in seven groups: group 1 (n = 10)--control, group 2 (n = 10)--pregnant female rats, group 3 (n = 10)--female rats submitted to cesarean, group 4 (n = 10)--female rats with natural childbirth, group 5 (n = 10)--virgin female rats with simulated trauma of childbirth, group 6 (n = 10)--female rats submitted to cesarean followed by simulation of childbirth trauma, and group 7 (n = 10)--female rats with natural childbirth followed by simulation of childbirth trauma. The average concentration of collagen and elastic fibers and the collagen/muscular fiber correlation in groups 1, 2, and 3 were similar and significantly inferior to groups 4, 5, 6, and 7. The average of muscular fibers was similar in groups 1, 2, and 3 and significantly superior to groups 4, 5, 6, and 7. Pregnancy and cesarean did not induce alterations in collagen, muscular, and elastic fibers. However, the vaginal delivery and simulation of childbirth trauma determined the decrease in muscular fibers and the increase in collagen and elastic fibers and the correlation collagen/muscular fiber.

Animals↗
PubMed2005

Prevalence and correlates of stress urinary incontinence during pregnancy: a survey at UNICAMP Medical School, São Paulo, Brazil.

The aim of this study was to evaluate the prevalence of stress urinary incontinence (SUI) in women in the third trimester of pregnancy. In total, 340 patients attending the Antenatal Clinic at the State University of Campinas (UNICAMP) were interviewed. Overall, 170 women (50%) presented SUI. Stress urinary incontinence did not correlate to either body mass index (BMI) or race. There was no correlation between parity and SUI, but when considering distinct types of effort, urine leakage on coughing (P = 0.0478) and laughing (P = 0.0046) were highly more frequent in multiparous women. One hundred eleven women had had only vaginal deliveries and 68 delivered by cesarean section. There was no difference between the two groups concerning incontinence, but multiparous women (> or = 4) who delivered exclusively vaginally demonstrated 2.0 times more chances to leak urine when compared to nulliparous women. This fact strongly suggests parity to be more relevant than delivery route as a risk factor to stress urinary incontinence. Nulliparous women presented with a high percentage (45.5%) of the symptom, emphasizing the elevated risk of SUI during first pregnancy.

Adult↗
PubMed2005

[Transobturator correction of cystocele].

OBJECTIVE: We present our initial experience with the Perigee system for anterior vaginal wall prolapses repair. MATERIAL AND METHOD: 15 patients with anterior vaginal wall prolapse (mean age: 62 years old) underwent implanted with Perigee system which is composed by a mesh for correcting central defect and four self-attached horns for correcting lateral defect. The implanted procedure consist of four steps: 1) lateral vaginal wall dissection as far as isquiopubic branch; 2) performance of two upper marks at genitofemoral fold and two lower marks at 2 cm laterally and 3 cm lower; 3) insertion of the upper needles parallel to the isquiopubic branch and connection with the mesh's "arms" plus insertion of the lower needles vertically and connection with mesh's "legs"; 4) to adjust the mesh free tension. The system POP-Q was used as an objective measure of correction rate. RESULTS: Preoperatively, the point Aa was 0.09. After 6 weeks and three months postoperatively was -3.00 and -2.73 respectively. Preoperatively, the point Ba was 1.73. After 6 weeks and three months postoperatively was -2.82 and -2.82 respectively. No major complications were presented. No vascular damage or significant bleeding was observed. CONCLUSION: The transobturator correction of cystocele is an attractive alternative. The initial good outcome may be expected to be long lasting.

Adult↗
PubMed2004

Urethral resistance measurement: a new method for evaluation of stress urinary incontinence in women.

The aim of this study was to evaluate a new method to measure urethral resistance among 66 women with urinary incontinence. A stainless steel sphere attached to a guide wire was developed. The sphere is inserted into the bladder and withdrawn through the urethra at a steady rate. Serial measurements with spheres of 5, 6 and 7 mm were performed. The mean urethral resistance as measured by the largest sphere (0.07+/-0.03) was significantly greater than that measured by the medium sphere (0.06+/-0.02, p<0.0001), which was significantly larger than that measured by the smallest sphere (0.04+/-0.01, p<0.0001). There was good correlation of urethral resistance with maximum urethral closure pressure (MUCP) by this technique, but no correlation with Valsalva leak point pressure (VLPP).

Adult↗
PubMed2002

Urodynamics in climacteric women with urinary incontinence: correlation with route of delivery.

The aim of this study was to compare the urodynamic findings among climacteric women complaining of urinary incontinence who had only vaginal deliveries with those who had only cesarean sections. The study group comprised 30 climacteric women with complaints of urinary incontinence consulting at the Menopause Outpatient Clinic, State University of Campinas, submitted to anamneses and complete urodynamic testing. Nineteen women had had only vaginal deliveries and 11 were delivered only by cesarean section. Vaginal delivery was significantly associated with a reduced normal and strong desire to void and maximum cystometric capacity compared to women who delivered only by Cesarean section. Detrusor instability was four to five times more frequent among women who had had only vaginal deliveries. There was no difference between the two groups concerning uroflowmetry parameters. Climacteric women with urinary incontinence who had had only vaginal deliveries are at a higher risk of urodynamic abnormalities.

Adult↗
PubMed2002

Urinary tract infections: pathogenesis and related conditions.

This paper deals with main aspects of pathogenesis of urinary tract infection (UTI). Bacterial and host-related factors such as defense mechanisms and predisposing factors are described. Special aspects of UTI in elderly patients and during pregnancy are discussed. Recurrent cystitis and prophylactic measures are also reported.

Aged↗
PubMed2000

Beta2-adrenergic receptor polymorphisms at codon 16, cardiovascular phenotypes and essential hypertension in whites and African Americans.

Beta2-adrenergic receptors (beta2-AR) contribute to cardiovascular regulation by influencing several functions and previous studies suggest that a decreased function of the beta2-AR may be involved in essential hypertension. Beta2-AR are polymorphic and certain polymorphisms of these receptors are of functional importance. We focus here on the Arg16-->Gly16 beta2-AR polymorphism, which shows enhanced agonist-promoted downregulation of the receptor and which, in two recent studies, yielded opposite results in terms of association with essential hypertension: an increased frequency of the Gly16 variant in African-Caribbean hypertensives and of the Arg16 variant in offspring of Norwegian white hypertensive parents. In the current study, we genotyped 243 subjects, including both African-American and white individuals, for codon 16 polymorphism and assessed blood pressure and cardiovascular function using impedance cardiography and pressor sensitivity to phenylephrine. We found similar patterns of cardiovascular function and expression of hypertension with the two genotypes of codon 16. There was no statistically significant difference in the overall allelic distribution of the two genotypes: among African-Americans, 51% of the hypertensives and 50% of the normotensives carried the Arg16 allele, whereas among the white subjects 40% of the hypertensives and 47% of the normotensives were carriers of the Arg16 allele. Although we observed a statistically significant increase in the Arg16/Gly16 heterozygotes in the African-American population, the Gly16 allele was not significantly increased in the African-Americans compared to whites. These findings indicate that the codon 16 polymorphisms are not associated with hypertension in a mixed American study population nor do they appear to substantially impact on a variety of hemodynamic variables.

Adult↗
PubMed2000

beta-adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells.

beta-Adrenergic receptor (betaAR) activation and/or increases in cAMP regulate growth and proliferation of a variety of cells and, in some cells, promote cell death. In the current studies we addressed the mechanism of this growth reduction by examining betaAR-mediated effects in the murine T-lymphoma cell line S49. Wild-type S49 cells, derived from immature thymocytes (CD4(+)/CD8(+)) undergo growth arrest and subsequent death when treated with agents that increase cAMP levels (e.g., betaAR agonists, 8-bromo-cAMP, cholera toxin, forskolin). Morphological and biochemical criteria indicate that this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells, which lack G(s)alpha and functional protein kinase A (PKA), respectively, betaAR activation of G(s)alpha and cAMP action via PKA are critical steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cAMP-induced apoptosis. We conclude that betaAR activation induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while overexpression of Bcl-2 prevents cell death. betaAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Comparative pharmacodynamics and pharmacokinetics of candesartan and losartan in man.

The angiotensin II antagonistic effects of candesartan and losartan were compared in-vivo after single and repeated doses. Effects were related to antagonistic activity in plasma. In this double-blind, crossover study, 12 healthy male volunteers received, in random order, daily oral doses of 8 mg candesartan cilexetil or 50 mg losartan for seven days. On day 1 and day 8, dynamics and kinetics were assessed up to 48 h after dosing. Antagonistic effect was determined from the antagonist-induced rightward shifts of the diastolic blood pressure response curves to exogenously administered angiotensin II measured as the dose ratio (DR). The antagonistic activity in plasma was measured using an ex-vivo/in-vitro radioreceptor assay. Specific high-performance liquid chromatography assays determined plasma concentrations of candesartan, losartan and its active metabolite EXP-3174. The pharmacokinetic properties of candesartan and losartan were comparable and antagonistic activity in plasma almost identical (ratio candesartan: losartan = 0.97 and 1-2 after single and multiple doses, respectively). However, the antagonistic effects of candesartan and losartan in-vivo were quite different. Twenty-four hours after single dosing with candesartan a clinically relevant rightward shift in the angiotensin II dose-response curve (DR= 3.2) occurred that was more pronounced than that following losartan administration (DR=2.1, ratio candesartan: losartan= 1.65). Twenty-four hours after multiple doses of candesartan or losartan, the values of the DR were 4.8 and 2.3, respectively (ratio candesartan: losartan = 1.94). The values of DR for candesartan were significantly higher compared with losartan between 6 and 36h after a single dose and between 3 and 24 h post-dose following multiple dose administration. A counter-clockwise hysteresis was apparent between antagonistic activity in plasma and antagonistic effect. Despite equivalent angiotensin II antagonistic activity in plasma, the pharmacodynamic effect of candesartan cilexetil was greater than that of losartan. Candesartan appeared to have a slower off-rate from the angiotensin AT1-receptor compared with losartan, nevertheless differences in distributional phenomena or the extent of insurmountable antagonistic activity cannot be ruled out.

Adult↗
PubMed1999

Variability in phenylephrine response and essential hypertension: a search for human alpha(1B)-adrenergic receptor polymorphisms.

Genetic polymorphisms in drug receptors, in particular adrenergic receptors, may contribute to intersubject differences in pharmacologic response. We tested patients and first-degree normotensive and hypertensive relatives of patients with essential hypertension and found substantial intersubject variability in blood pressure response to infusion of the alpha(1)-adrenergic agonist phenylephrine. Because response to phenylephrine depends upon interaction with alpha(1B)-adrenergic receptors, we tested whether polymorphisms in this receptor contribute to the variable responses. Accordingly, we developed a polymerase chain reaction-based method, generating four exon-spanning fragments, to identify polymorphisms in the coding sequence of the two exons of the human alpha(1B)-adrenergic receptor. We sequenced the entire coding sequence of exon 1 from 51 subjects and exon 2 from 16 of these 51 subjects. Compared with the published sequence for the alpha(1B)-adrenergic receptor, we found one amino acid addition in exon 2 at position 368 (Arg) and one substitution (Arg371Gly) in all subjects. We thus suggest we have defined the correct coding sequence of the human alpha(1B) receptor. We found two "silent" polymorphisms in exon 1, one of which occurred in 3 of 51 subjects. These polymorphisms were unrelated to blood pressure status or response to phenylephrine. The 95% confidence intervals for expression of polymorphisms in exons 1 and 2 were 0 to 11%. Our data reveal that although phenylephrine response varies in humans, frequent polymorphisms in the coding sequence of the human alpha(1B)-adrenergic receptor appear not to account for this variation or for the increased blood pressure in patients with essential hypertension.

Adult↗
PubMed1998

PCR-based methods for identifying genetic variations in human alpha1B- and beta2-adrenergic receptors.

alpha- and beta-adrenergic receptors belong to the superfamily of G-protein-coupled, seven transmembrane domain receptors and regulate a variety of cellular processes. Previous studies have demonstrated that changes in the amino acid sequence can result in substantial changes in the function of the receptors and it has been suggested that there may be an association between different disease states and the altered structure of alpha- and beta-adrenergic receptors. Accordingly, we have developed a simple PCR method for the identification of polymorphisms in the coding sequences of the human beta2-adrenergic receptor and the alpha1B-adrenergic receptor. This method may be useful for screening individual patients or at-risk populations for endocrine-metabolic disorders, as well as for asthma, cardiovascular disorders, and neuropsychiatric diseases.

Base Sequence↗
PubMed1998

Angiotensin II antagonism and plasma radioreceptor-kinetics of candesartan in man.

AIMS: The pharmacodynamic properties of the angiotensin II antagonist candesartan in humans were assessed from the rightward shifts of angiotensin II dose-effect curves (Schild regression technique). The pharmacokinetic characteristics were determined by radioreceptor assay (r.r.a.) and h.p.l.c. METHODS: Twelve healthy male volunteers received single oral doses of 4, 8 and 16 mg candesartan cilexetil and placebo. Plasma was obtained for h.p.l.c. and r.r.a. (receptors: rat lung; radioligand: [125I-Sar1Ile8]-angiotensin II). Before and up to 24 h post dosing angiotensin II was infused in ascending dose steps until blood pressure (systolic and/or diastolic) increased by +25 mmHg. Individual angiotensin II dose-effect curves were fitted according to an Emax model and dose ratios (DR) calculated from the antagonist induced rightward shifts. RESULTS: Candesartan, the active metabolite of candesartan cilexetil, declined from peak concentrations at about 4 h with a t1/2 of about 6 h. A linear relation (slope 1) between h.p.l.c. and r.r.a. data revealed that there is no other active metabolite. DR at 6-9 h post dosing reached a maximum of about 30 and at 24 h still amounted to 4-7, indicating the persistence of a relevant antagonistic effect in vivo. The apparent Ki-doses (derived from Schild regression plots) indicated a high potency (1.9 mg at 24 h) and slow decline of effect. Between plasma concentrations and antagonistic effect a counterclockwise hysteresis was visible. CONCLUSIONS: A longer persistence of the antagonistic effect at the receptor site than expected by the presence in plasma indicates a slow off-rate of candesartan cilexetil from in vivo receptors. This provides an additional rationale for the observed 24 h therapeutic activity of candesartan cilexetil.

Administration, Oral↗
PubMed1997

Repeated lipoinjections for stress urinary incontinence.

A total of 30 women with stress incontinence underwent periurethral injection of autologous fat under spinal anesthesia. The fat was harvested from the abdominal wall by liposuction. Preoperative evaluation consisted of history, physical examination, and urodynamic evaluation. For study purposes, some patients also underwent bladder and urethral ultrasonography and magnetic resonance imaging studies. The first 13 patients received a single periurethral lipoinjection, and the following 17 patients received sequential injections when needed at 3-month intervals. Results were assessed by subjective questionnaire performed at 3 and 12 months. All patients had intrinsic sphincteric deficiency. Of the first group, there were only four patients (31%) cured after 1 year of follow-up. On the other hand, in the group that received repeated injections, there were 11 patients (64%) cured with a mean of two injections at 1-year follow-up. Our results show that this procedure warrants continued clinical investigation because it may be useful in selected cases of urinary stress incontinence.

Adipose Tissue↗
PubMed1997

Pharmacodynamic and pharmacokinetic properties of an angiotensin II receptor antagonist--characterization by use of Schild regression technique in man.

OBJECTIVE: The pharmacodynamic properties of a new angiotensin II receptor antagonist (BAY 10-6734) in humans were to be quantitatively characterized from the rightward shifts of the agonist dose-response curves after administration of different doses of the antagonist. METHODS: 24 healthy male volunteers received single oral doses of 20-300 mg BAY 10-6734. Before and up to 23 h post dosing (p.d.) plasma was obtained for HPLC measurement of parent compound and active metabolite BAY 10-6735. Exogenous angiotensin II was infused in increasing dose steps until blood pressure had increased by +25 mmHg. Angiotensin II dose-response curves were fitted individually using the sigmoidal Emax model. From the antagonist-induced rightward shifts, as compared to a premedication curve, dose ratios (DR) were determined and DR-1 plotted versus applied dosages and measured plasma concentrations. From these Schild regression plots the fictive doses and concentration (Ki) inducing a DR-1 = 1, i.e. a 2-fold shift in agonist dose-response curves, were derived. The "doubling (t2.0) time" of the apparent Ki doses was calculated. RESULTS: BAY 10-6734 dose-dependently induced rightward shifts of the angiotensin II blood pressure response curves, mean maximum DR at 2 h p.d. ranged from 42 (80 mg) to 216 (300 mg), and at 23 h p.d. decreased to about 2 (80 mg) to 4 (300 mg). Pharmacodynamic (3.4-4.6 h) and pharmacokinetic half-lives (3.4-4.3 h) were nearly identical. Apparent Ki doses increased from about 1-2 mg at 2 h p.d. to about 80-100 mg at 23 h p.d., their time course revealed a doubling (t2.0) time of 3.5-3.8 h. A Ki concentration of about 10 micrograms/l was obtained for the active metabolite BAY 10-6735. CONCLUSIONS: Oral administration of BAY 10-6734 in man antagonized angiotensin II dose blood pressure response curves in a dose-dependent manner. The time kinetics of the pharmacodynamic effect, derived from the decay of DR-1 values, as well as the doubling time of the apparent Ki values well agreed with the pharmacokinetic half-life. Schild regression revealed competitive angiotensin II antagonistic properties within the dose/concentration range tested. This technique was shown to be an adequate means to evaluate pharmacodynamic potency and kinetic behavior of an angiotensin II receptor antagonist in vivo.

Administration, Oral↗
PubMed1992

[The histochemical formation of the myoadenylate deaminase reaction in human skeletal musculature].

Muscle biopsies from control subjects, patients with neuromuscular diseases and premature infants and neonates were investigated for myoadenylate deaminase activity (MAD) by histochemistry. A histochemically picture of MAD-deficiency is more frequently then the clinically defined MAD-deficiency syndrome with an autosomal recessive pattern of inheritance. The high incidence of the carrier state, secondary MAD-deficiency and connections with other diseases are the causes. An individual predisposition for loading crisis of these patients in a high physical stress situation is probable.

AMP Deaminase↗