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Biomedical subjects

R Valentine

Publications and source records attributed to R Valentine.

At least 37 records · Page 2Linked to original sources
PubMed1993

Testicular degeneration and spermatid retention in young male rats.

The incidence of spontaneous testicular atrophy and its morphological changes in relation to stage-specific spermatogenesis were investigated in young Crl:CD/BR male rats at 10-12 wk of age used as controls for toxicity screening during 1983-1990. The incidence of testicular degeneration was 2.5% (5/197) in control rats used for oral toxicity studies and 9.4% (31/327) in rats used for inhalation studies. The epididymal tubules of rats with testicular degeneration had exfoliated germ cells and low sperm density. The high incidence of testicular degeneration observed in the control rats used in inhalation studies may be related to the stress associated with immobilization in the restrainer during nose-only exposure conditions. The severity of testicular degeneration in the inhalation studies was mostly minimal. In these minimally affected testes, mature spermatids (step 19) were retained within normal-appearing germinal epithelium at spermatogenic stages IX-XIV. Also, eosinophilic globular bodies (EGBs) were formed with elongated or mature spermatids throughout all spermatogenic stages, but the general architecture of germinal epithelium was normal in appearance. By electron microscopy, EGBs were sequestered necrotic spermatids, and the germ cell degeneration was associated with cytoplasmic vacuolation of Sertoli cells. In moderate testicular degeneration, markedly decreased maturing spermatids (steps 15-19) and a slight depletion of round spermatids were observed in stages I-VIII. In severe testicular degeneration, seminiferous tubules were lined with 1-2 layers of round spermatids and spermatocytes with giant cell formation. The round spermatids served as a marker to identify spermatogenic stages (I-VIII) of the atrophic tubules. Also, in severe testicular degeneration, tubules in spermatogenic stages X-XIV had no elongated spermatids, and spermatocytes were exfoliated with occasional giant cell formation. Many seminiferous tubules were lined with only 1-2 layers of spermatocytes, and specific germ cell markers were not present.

Administration, Inhalation↗
PubMed1993

Dimethylformamide pharmacokinetics following inhalation exposures to rats and mice.

Whole-body inhalation exposures to N,N-dimethylformamide (DMF) were conducted with rats and mice. The exposure concentrations were 10, 250, and 500 ppm DMF. The exposure routines consisted of single 1-, 3-, or 6-hour exposures and ten 6-hour exposures (ten exposure days in 2 weeks). Area under the plasma concentration curve (AUC) values were determined following exposure for DMF and "N-methylformamide" ["NMF" represented N-methylformamide plus N-(hydroxymethyl)-N-methylformamide (DMF-OH)]. The DMF AUC values increased 8- and 29-fold for rats and mice, respectively, following single six-hour exposures to 250 and 500 ppm DMF. These data are indicative of saturation of DMF metabolism. Peak "NMF" plasma concentrations for rats and mice, following single 6-hour exposures, did not increase as DMF exposure concentrations increased from 250 to 500 ppm. In addition, the "NMF" plasma levels in rats following a single 6-hour 500 ppm DMF exposure did not decay by 24 hours post exposure. These "NMF" plasma data also indicate saturation of DMF metabolism. Multiple exposures to 500 ppm DMF resulted in a 3- and 4-fold reduction in DMF AUC values for rats and mice, respectively, compared to AUC values following a single six-hour 500 ppm DMF exposure. This indicates enhanced metabolism of DMF resulting from multiple 500 ppm DMF exposures and together with saturation of DMF metabolism suggest using exposure levels below 500 ppm in a chronic bioassay. Selected plasma samples were simultaneously assayed for NMF and DMF-OH. The "NMF" values consisted of between 30 to 60 percent DMF-OH depending upon the exposure group (conversely NMF represented 30 to 60 percent of the "NMF" levels). Urinary analysis of all samples revealed DMF-OH represented over 90 percent of the summed DMF, DMF-OH and NMF quantities.

Administration, Inhalation↗
PubMed1992

Nasal lesion development and reversibility in rats exposed to aerosols of dibasic esters.

This study was conducted to investigate the initial tissue damage, morphogenesis, and reversibility of nasal lesions induced by the inhalation of dibasic esters (DBE). Young male rats were exposed, nose-only, to an aerosol/vapor mixture of DBE at a concentration of 5,900 mg/m3 for 4 hr and subsequently killed at 1, 4, 7, 14, 21, and 42 days after exposure. Nasal lesions were distributed along major inspiratory airflow routes. Widespread epithelial denudation occurred in the anterior nasal cavity, but the lesions were confined to the dorsal meatus, adjacent the nasal septum, and the lateral middle meatus in the mid-anterior nasal cavity. The lesions were markedly less severe in the posterior nasal cavity and sharply confined to the tips of dorsal ethmoturbinates and adjacent nasal septum. The damaged cuboidal/nonciliated and respiratory epithelium in the anterior nasal cavity regained a normal structure by 4 and 7 days postexposure, respectively. The regeneration of damaged olfactory epithelium was related to the severity of initial tissue damage. Slightly damaged epithelium regained a normal appearance within 1-2 weeks, but the extensively denuded epithelium of the dorsal meatus in the anterior nasal cavity failed to regain a normal structure by 6 weeks. The sustentacular cells of the olfactory epithelium appeared to be the initial site of DBE nasal injury. In the early stages of regeneration, the epithelium was repaired by proliferating stem cells derived from basal cells. Numerous mitotic figures and bromodeoxyuridine labeling were found in the regenerating basal cells, stem cells, and sustentacular cells at 4 and 7 days. As repair processes advanced, the numbers of olfactory neurons and vesicles were increased with a proportional decrease in stem cells.

Adipates↗
PubMed1991

Pathogenesis and reversibility of retinopathy induced by 1,4-bis (4-aminophenoxy)-2-phenylbenzene (2-phenyl-APB-144) in pigmented rats.

Pigmented male rats were administered a suspension of 0, 25, or 100 mg/kg 2-phenyl-APB-144 in corn oil by gavage. The rats were killed at 4 and 12 h, and at 1, 2, 4, 7, 14, 28, 57, or 84 days after a single oral administration. The primary site of retinopathy appeared to be the retinal pigment epithelial (RPE) cells. The RPE cells showed necrosis within 12 h post-exposure (PE) at 25 mg/kg and within 4 h PE at 100 mg/kg. Subsequently, photoreceptor outer segments (POS) were disrupted with a hyperplastic RPE cell response within 2 days PE. Intact photoreceptor inner segments (PIS) and RPE cells apposing closely with distal POS were important determinants for reversibility of the damaged POS. The damaged RPE cells were regenerated prior to restoration of normal POS. At 25 mg/kg, both the RPE cells and POS were damaged, but PIS were intact. The damaged POS were regenerated from intact PIS with closely apposing RPE cells. By 14 days PE, the damaged POS had partially regenerated and attained approximately one third to one half of their normal length. By 57 and 84 days PE, the damaged retina had regained an essentially normal structure. In contrast, at 100 mg/kg, the POS and PIS were extensively disrupted, with marked RPE cell hyperplasia after 7 days PE resulting in the formation of multiple retinal arcades (foldings), and rosettes by 14 days PE. Subsequently, retinal arcades and rosettes gradually disappeared as the result of extensive loss of PIS and POS with progressive migration of photoreceptor nuclei toward the Bruch's membrane after 28 days PE. Focal regeneration of POS was observed by 57 days PE where intact PIS and a single layer of regenerated RPE cells were apposed closely with distal POS. The POS regeneration did not occur where the RPE cells were denuded or hyperplastic RPE cells were present. The hyperplastic RPE cells were devoid of slender apical processes, closely enclosing the distal POS. Approximately 20-30% of the retina had partially regained a normal structure by 84 days PE.

Animals↗
PubMed1991

An open label trial of alprazolam in comorbid irritable bowel syndrome and generalized anxiety disorder.

BACKGROUND: The irritable bowel syndrome (IBS) is very prevalent and psychiatric comorbidity runs high. A significant proportion of generalized anxiety disorder (GAD) patients manifest concurrent IBS. METHOD: We conducted a 14-week, open-label trial of the triazolobenzodiazepine alprazolam in 32 patients with comorbid generalized anxiety and IBS. At the end of a 2-week placebo run-in, eligible subjects received 6 weeks of active drug therapy. RESULTS: Ninety-four percent of subjects (N = 25) had a full or partial anxiolytic response at the 6th treatment week (p less than .001). Eighty-nine percent (N = 24) experienced a concomitant reduction in IBS severity. For the majority, these dual benefits were still evident at the conclusion of a 4-week drug taper (p = .05) and achieved a trend (p = .07) at a 4-week postdrug discontinuation visit. CONCLUSION: Alprazolam was safe, effective, and well tolerated during the acute treatment of comorbid GAD and IBS; only a limited posttreatment rebound was observed.

Alprazolam↗
PubMed1990

Retinotoxicity of 1,4,-bis(4-aminophenoxy)-2-phenylbenzene (2-phenyl-APB-144) in albino and pigmented rats.

Albino and pigmented strains of rats were administered 0, 5, 25, 100 or 500 mg/kg 2-phenyl-APB-144 by gavage and were killed 14 days later. Although no ocular lesions were found in rats dosed at 5 mg/kg, similar dose-related retinopathy was found at 25, 100, or 500 mg/kg in both albino and pigmented rats. The primary target site appeared to be retinal pigment epithelial (RPE) cells and photoreceptor outer segments (POS). At 25 mg/kg or greater, multifocal retinal detachment with disrupted POS occurred where the RPE cells showed necrotic changes and contact loss with POS due to fragmentation of apical processes in the RPE cells. Also, RPE cells showed hyperplasia, migration, and phagocytic activity toward disrupted POS. The photoreceptor nuclei (outer nuclear cells) were displaced into the areas occupied by disrupted POS. At 100 or 500 mg/kg, multifocal or diffuse disruption of POS and photoreceptor inner segments (PIS) was observed with markedly proliferating RPE cells. The photoreceptor nuclei were disorganized, less numerous, and necrotic. Some photoreceptor nuclei directly apposed the RPE cells or Bruch's membrane due to the absence of both POS and PIS. The cytoplasm of RPE cells was loaded with phagosomes, disrupted lamellar discs, myelin bodies, and lysosomal residual bodies. The morphological changes appeared to be related to lysosomal dysfunction of the RPE cells. The presence of melanin pigment in the RPE cells did not appear to be the primary factor in the development of the retinopathy.

Albinism↗
PubMed1989

Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats.

Male rats were exposed to 0, 110, 370, or 1100 ppm bis(2-methoxyethyl)ether (diglyme) 6 h/day, 5 days/week for 2 weeks. One group of male rats was exposed to 300 ppm 2-methoxyethanol (2-ME) for 2 weeks as a positive control. Exposed rats were killed after 10 days of exposure and 14, 42, or 84 days post-exposure (PE), respectively. At 110 ppm diglyme, spermatocytes in pachytene and meiotic division at spermatogenic stages XII-XIV were mainly affected. At 370 ppm diglyme, affected germ cells were similar to those seen at 110 ppm diglyme, but round spermatids at spermatogenic stages I-VII were also affected. The testes regained normal spermatogenesis by 84 days PE. At 1100 ppm diglyme or 300 ppm 2-ME, marked testicular atrophy was found affecting all spermatogenic stages. Damaged seminiferous tubules were lined with regenerating pachytene spermatocytes at 14 days PE and with spermatocytes and round spermatids after 42 days PE. Most but not all testes in rats exposed to 300 ppm 2-ME or 1100 ppm diglyme had normal morphology after 84 days PE. Based on the observation of germ cell damage, spermatozoa population in the epidymal tubules, reversibility of spermatogenesis after various PE periods, testicular toxicity induced by 300 ppm 2-ME was more severe than that seen at 370 ppm diglyme but was slightly less remarkable than that of 1100 ppm diglyme.

Animals↗
PubMed1986

Primary aldosteronism due to a malignant ovarian tumour.

The case of a woman with autonomous aldosteronism, hypertension, and malignant ovarian tumour is reported. Hormone studies revealed high plasma aldosterone levels, and low plasma renin concentration. Following surgical removal of a malignant sex cord stromal tumour, the hyperaldosteronism regressed, and the hypertension improved. Subsequently the tumour recurred, as did hyperaldosteronism.

Aldosterone↗
PubMed1985

An in vitro system for exposure of lung cells to gases: effects of ozone on rat macrophages.

A test system was developed for the in vitro exposure of lung cells to gases. The exposure system was used to evaluate ozone (O3) injury to pulmonary alveolar macrophages (PAM) obtained from Sprague-Dawley rats by bronchopulmonary lavage. Ozone exposures were conducted within temperature-controlled stainless-steel and Plexiglas chambers that contained glass petri dishes affixed to a revolving, inclined platform. Cell exposures were accomplished by rotation of the platform at 1 rpm to alternately expose PAM monolayers to culture media and O3. The system provided stable, O3-containing atmospheres and permitted simultaneous in vitro exposures at three O3 concentrations. In vitro exposure of PAM monolayers for 2 h at chamber concentrations ranging from 0.2 to 6.1 ppm O3 was associated with a significant, concentration-related reduction of latex-bead phagocytosis in rotated PAM cultures. In contrast, PAM that were similarly exposed in nonrotated dishes placed horizontally and covered with a stationary layer of media (1.5 mm depth) were not affected. Other parameters of cell function, including PAM viability and adherence, were unchanged compared to unexposed or horizontal, nonrotated controls. The inability to observe adverse effects among the nonrotated cultures is consistent with the impaired diffusion of O3 through the comparatively thick media overlay in stationary cultures. The in vitro system provides a realistic simulation of lung cell exposure to O3 and represents a useful model to study the toxicity of gases on cultured cells.

Animals↗
PubMed1985

A rare pelvic mass: osteosarcoma of the body of the uterus.

A rare, enormous, unresectable, osteosarcoma of the uterus is reported. This obstructed ureters, enclosed rectum, bladder, aorta and vena cava, and metastasized to peritoneum, lungs and liver causing death of the patient by renal and pulmonary failure.

Female↗
PubMed1985

Thyroxine binding and TSH in recurrent depressive episodes.

Evidence of a link between recurrent affective disorders and the hypothalamic-pituitary-thyroid (HPT) axis has been frequently reported. The clinical course of 40 recurrent major depressive patients was monitored over 2 years with respect to several parameters of thyroid function. Patients entering a depressive recurrence manifested lower free versus bound thyroxine quotients and had higher TSH secretion. A dynamic HPT axis response may enhance the clinical outcome of acute depression during continuation pharmacotherapy.

Adult↗
PubMed1984

Characteristics of bovine alveolar macrophage elastase.

Lavage of isolated bovine lung lobes was used to retrieve pulmonary alveolar macrophages (PAM). Nominal yields of 72 million viable PAM were routinely obtained using 500 ml of calcium- and magnesium-free phosphate-buffered saline. Bovine PAM readily attached to glass coverslips and within 24 hours, provided cell monolayers consisting exclusively of macrophages. Bovine PAM synthesized and secreted a calcium-dependent elastase in serum-free media. Optimal proteolytic activity using a radiolabeled elastin substrate was observed at pH 7.6. The elastase was insensitive to synthetic peptide chloromethyl ketone elastase inhibitors and to the serine protease inhibitor, phenylmethylsulfonyl fluoride. Enzyme activity, however, was effectively inhibited by the metal chelator, ethylenediaminetetraacetic acid, or suppressed by inhibition of protein synthesis with cycloheximide.

Animals↗
PubMed1984

Pulmonary clearance of intratracheally administered 63Ni3S2 in strain A/J mice.

The pulmonary clearance of particulate 63Ni3S2 was evaluated in strain A/J mice following the intratracheal instillation of 3 microCi of 63Ni3S2 (1.66 micron, mass median diameter). Lung and tissue burdens were determined from serially sacrificed animals using scintillation counting techniques. Lung clearance over the 35-day observation period could be separated into two distinct components with initial and final phase biological half-times corresponding to 1.2 and 12.4 days, respectively. Radioactivity was detected in the blood, liver, kidney, and femur within 4 hr, and was eliminated at rates comparable to that in the lung. Excretion involved primarily urinary (60% of dose eliminated) but also fecal (40% of dose eliminated) pathways. The data are consistent with the relatively rapid translocation, solubilization, and elimination of particulate 63Ni3S2 from the body.

Animals↗
PubMed1983

Morphological and biochemical features of elastase-induced emphysema in strain A/J mice.

Elastase-induced animal models of pulmonary emphysema are potentially useful to study the physiological, anatomical, and biochemical injuries associated with emphysema. After the endotracheal instillation of porcine pancreatic elastase (0.15 or 0.30 mg elastase per 100 g body weight) into strain A/J mice, selected biochemical and morphometric indices od lung damage were examined. Elastase produced extensive air space enlargement without appreciable mortality. Lesions involving the lung parenchyma distal to the terminal bronchioles were observed within 2 weeks and possessed features resembling panlobular and centrilobular emphysema. Morphometric analyses of emphysema indicated that after the acute phase of tissue damage and repair, the lesions stabilize without further deterioration of alveolar structure. Increased lung elastin synthesis was noted following endotracheal elastase, resulting in lung elastin levels 30% higher than controls 8 weeks after treatment. Minimal alterations to lung DNA and protein levels indicated that elastase produced specific lung lesions exclusive of inflammation and edema.

Animals↗
PubMed1983

Thermal modification of chrysotile asbestos: evidence for decreased cytotoxicity.

Many asbestiform minerals exhibit temperature-dependent thermoluminescence. Since thermoluminescence involves electronic transitions within crystalline materials, the effect of temperature on asbestos cytotoxicity was evaluated. Heat pretreatment of Canadian chrysotile asbestos reduces its cytotoxicity towards cultured human fibroblasts and bovine alveolar macrophages. When monitored 44 hr after the addition of either 200 degrees C or 400 degrees C heat-pretreated asbestos, alveolar macrophage viability was approximately 40% higher than comparable amounts of unheated asbestos. Similarly, asbestos toxicity, expressed as fibroblast growth inhibition, was inversely related to the asbestos pretreatment temperature in the following manner, 70 degrees C greater than 200 degrees C greater than 400 degrees C = unexposed fibroblast controls. Pretreatment of chrysotile asbestos to 400 degrees C reduced its adsorptive capacity for bovine serum albumin by 25%. Furthermore, asbestos heated to 200 degrees C followed by irradiation with 4 MeV X-rays (4500 rads) resulted in reactivation of asbestos cytotoxicity. Scanning electron microscopy indicated that the ratios of free to fiber-associated alveolar macrophages and the fiber fragment size distributions were unaffected by either heat pretreatment or X-ray irradiation. These observations strongly suggest that the surface charge characteristics and electronic state of asbestos fibers may be responsible for its biological activity.

Adsorption↗