Renin, sodium-retaining and sodium-excreting hormones and experimental renal hypertension.
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Biomedical subjects
Publications and source records attributed to S S Howards.
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The effects of the male antifertility agents alpha-chlorohydrin, 5-thio-D-glucose, and 6-chloro-6-deoxy-D-glucose on sugar transport (3H-3-O-methyl-D-glucose and 3H-2-deoxy-D-glucose) across the rat caput epithelium was studied in vivo and in vitro. The compound alpha-chlorohydrin reduced sugar transport uptake in vivo but not in vitro, whereas 5-thio-D-glucose and 6-chloro-6-deoxy-D-glucose were both effective in vivo and in vitro. The mechanism of action of these compounds on sugar movement across the caput epithelium is probably complex. Direct competition for the glucose carrier situated on the basolateral membrane and intratubular effects are suggested. Thirty-day injections of 5-thio-D-glucose or alpha-chlorohydrin did not have adverse effects on sugar transport or the permeability of the blood-testis and blood-epididymis barriers as assessed by an in vitro technique.
The maturation of spermatozoa in the epididymis is dependent upon the presence of androgens. This study examined the effects of androgen suppression by estradiol valerate on the elemental composition of the intraluminal fluids of the testis and epididymis. In the fluid from the caput epididymidis, the concentrations of sodium (106.1 +/- 3.4 to 182.8 +/- 16.9 mmol/1, P less than 0.01) and chloride (16.5 +/- 2.2 to 79.3 +/- 10.8 mmol/1, P less than 0.01) rose after treatment with estradiol valerate. By contrast, this treatment reduced the concentrations of phosphorus (63.7 +/- 1.6 to 47.8 +/- 3.2 mmol/1, P less than 0.01), sulfur (18.4 +/- 1.0 to 10.8 +/- 1.0 mmol/1, P less than 0.01), calcium (0.93 +/- 0.09 to 0.50 +/- 0.07 mmol/1, P less than 0.01), and magnesium (2.21 +/- 0.41 to 0.76 +/- 0.16 mmol/1, P less than 0.01). In the distal cauda epididymidis, the concentration of chloride rose after treatment with estradiol valerate (24.4 +/- 1.7 to 54.9 +/- 3.9 mmol/1, P less than 0.01), but the concentrations of the other measured elements (sodium, potassium, phosphorus, calcium, magnesium, and sulfur) were not altered by estrogen treatment. In rete testis fluid the concentration of phosphorus fell (2.00 +/- 0.30 to 0.67 +/- 0.12 mmol/1, P less than 0.01), while that of calcium rose (0.66 +/- 0.15 to 1.55 +/- 0.21 mmol/1, P less than 0.01). Estrogen treatment did not appear to affect the elemental composition of seminiferous tubular fluid or serum. Therefore, estradiol valerate had a marked impact on the elemental composition of luminal fluid only in the caput epididymidis--where sperm maturation is initiated--and a minor effect on that of cauda epididymidal fluid--in which mature spermatozoa are stored.
Hypophysectomized male rats were administered LH or LH + FSH for 14 days and subjected to in vivo micropuncture collection of reproductive tract fluids to determine if FSH alters the compartmentalization of testosterone in the rat testis or of 5 alpha-dihydrotestosterone (DHT) in the epididymis. Testosterone and DHT concentrations were determined in cardiac blood serum, testicular venous serum, testicular interstitial fluid, and seminiferous tubule fluid, and in intraluminal fluid and tissue extracts from the caput and cauda epididymidis. Testosterone is the predominant androgen in the testis, and compared with control values, concentrations in venous sera, interstitial fluid, and tubule fluid were returned to values indistinguishable from controls by supplementation with 24 micrograms LH/day. 24 micrograms LH + 24 micrograms FSH/day did not augment the intratubular partition of testosterone. Epididymal DHT values were returned to control levels by LH alone, but additional supplementation with FSH significantly increased DHT from the caput epididymidis even further. It is speculated that FSH does not alter the compartmentalization of androgens in the rat testis, but may play a role in retaining androgens in the epididymis.
The effects of varicocele and varicocele repair on testicular blood flow, temperature, sperm counts, and sperm motility were assessed in adult male rats. The duration of the experimental varicocele and the varicocele repair were three and two times as long, respectively, as that studied previously. Varicoceles were created by partial ligation of the left renal vein and repairs were accomplished by high ligation of the left spermatic vein. Testicular blood flow was determined by using the radiolabeled microsphere technique. Testicular temperature was taken via needle probe thermometer. Sperm samples were obtained by micropuncture of the cauda epididymidis, and were counted on a hemacytometer and observed for motility under the light microscope. Varicoceles were studied 100 days after their creation. Repairs were performed on varicoceles that had lasted 100 days and the animals were studied 60 days after repair. Mean testicular blood flow (ml/100 g tissue/min) was significantly increased (P less than 0.05) in animals with varicocele (left testis (LT) = 42.2 +/- 1.1, right testis (RT) = 39.1 +/- 1.2) when compared with normal controls (LT = 29.3 +/- 1.6, RT = 29.6 +/- 1.7), animals with varicocele repair (LT = 30.7 +/- 1.3, RT = 30.0 +/- 1.6), or sham-operated animals (LT = 29.7 +/- 1.4, RT = 31.1 +/- 1.4).(ABSTRACT TRUNCATED AT 250 WORDS)
The occurrence of spermatic granulomas of the vas deferens was studied in Lewis rats at intervals up to 7 months after vasectomy or vasectomy followed 3 months later by vasovasostomy. The incidence of granuloma progressed with time to involve one or both tracts in 100% of vasectomized rats. In addition, the majority of animals developed new granulomas after vasovasostomy, even though fluid flow through the reconnected vas deferens was demonstrated in vitro. When individual tracts were analyzed, the weight of the testis was related to ipsilateral spermatic granuloma formation in both vasectomy and vasovasostomy groups at 3 and 4 months after initial operation. Testes were small in the absence of a granuloma but similar to those of sham-operated rats if a granuloma was present. The possible protective effect of spermatic granuloma formation on the testis is discussed.
Unilateral varicocele has been associated with diminished male fertility in humans and with bilateral physiologic and histologic changes in the testis of humans and laboratory animals. In particular, left varicocele in Sprague-Dawley rats results in bilateral increases in testicular temperature and blood flow. The mechanism by which unilateral varicocele can cause testicular changes is not known. The purpose of the present study was to determine whether or not the presence of either the ipsilateral or contralateral testicle is necessary for these effects of the varicocele to occur in the opposite testis. Varicoceles were created in adult, male rats by partial constriction of the left renal vein. Bilateral testicular blood flow was measured by a radiolabelled microsphere distribution technique and testicular temperature was taken with a needle probe thermometer. Right or left orchiectomies were performed on selected animals at the time of surgery to establish the unilateral left varicocele. Animals were studied 30 days after surgery. Mean testicular blood flow was significantly increased (P less than 0.01) in all animals having a left varicocele when compared with animals not having a varicocele regardless of whether a unilateral orchiectomy was performed. Likewise, the mean difference between intraabdominal temperature and intratesticular temperature (delta T) was significantly decreased in all groups of animals having varicoceles when compared with groups without varicoceles whether or not an orchiectomy had been performed. Thus, the studied bilateral effects of left-sided, experimental varicocele in the rat are not dependent upon the presence of a left testicle.
An indirect enzyme-linked immunosorbent assay (ELISA) was employed to monitor antisperm autoantibodies in 16 Lewis rats for up to 36 weeks following vasectomy. This assay was capable of discriminating all prevasectomy from postvasectomy sera at a 1:16 dilution. Weekly serum samples were obtained for the first 13 weeks and bimonthly samples thereafter. Half of the animals developed a positive antisperm autoantibody response by the end of the first postoperative week. By the end of the second week, 81% of the animals had positive responses. The greatest proportion (88%) of animals having a positive response over the course of the study was found at the end of the seventh postoperative week and the highest mean absorbance value for all 16 animals was observed at this time. Only 25% of the animals had positive responses for antisperm autoantibody at the end of the 35th week of the study. These findings indicate that circulating antisperm autoantibodies arise in the Lewis rat earlier than has been generally appreciated. The time course is similar to that of antibody titers to infectious agents or arising from inoculation of rats with spermatozoa. These findings on autoantibody levels in the Lewis rat are compared with the dynamics of antisperm autoantibody formation in man.
Multiple sclerosis patients with bladder dysfunction are prone to have an asymptomatic urinary tract infection. Because bladder function abnormalities occur at some time in 70% to 90% of multiple sclerosis patients, a quantitative estimate of the bacterial concentration in the urine as well as a culture is mandatory. Treatment of bladder dysfunction or infection will vary according to the post-voiding residual volume. A patient with multiple sclerosis and asymptomatic urinary tract infection is reported that highlights strategies for the diagnosis and treatment of the urinary tract infection.
The purposes of this report were to describe a successful treatment of a burn injury in a patient with multiple sclerosis as well as to outline specific aspects of therapy that contributed to minimizing the risk of complications in this challenging patient. Multiple sclerosis is the leading cause of neurologic morbidity and death among young adults. It is an inflammatory disease of the central nervous system that involves the autonomic and somatic components and is characterized by a primary destruction of myelin. The demyelinated nerves exhibit an increased temperature sensitivity that accounts for the adverse effects of elevated core temperature on the neurologic signs and symptoms of this disease. Because burn injury, infection, and vigorous exercise elicit an elevation of core temperature with an accompanying deterioration in neurologic function, lowering the elevated core body temperature is mandatory. The dysautonomias of multiple sclerosis may be as devastating as their somatic counterparts and may have life-threatening implications. In recent years, advances in our understanding of the pathophysiology of central nervous system dysfunction have enabled physicians to improve dramatically the management of symptoms in multiple sclerosis without significantly altering the progressive long-term course of the disease.
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The appearance of serum antisperm antibodies was studied during the maturation of rats in which the vas deferens was obstructed prepubertally. Vasa deferentia were ligated and divided bilaterally in 10-day-old Lewis rats, while control animals received a sham operation at the same age. At ages between 14 and 128 days, blood samples were assayed for antisperm antibodies using an enzyme-linked immunosorbent assay. There were no differences between obstructed and sham-operated groups in mean antisperm antibodies from 14 through 56 days. However, in 91- and 128-day-old rats mean antisperm antibody levels were much higher in obstructed than in control animals. This rise in antisperm antibodies occurred several weeks after the development of spermatids in the testes between 23 and 46 days. The presence of elevated antisperm antibodies in obstructed animals followed temporally the appearance of sperm throughout the lumen of the entire epididymis and the formation of spermatic granulomas. The results in this model suggest that consideration be given to repair of injured or obstructed vas deferens prior to puberty to forestall development of antisperm antibodies, as well as the formation of spermatic granulomas.
Sperm protein autoantigens recognized by serum antisperm autoantibodies during development following vas deferens obstruction were studied using western blot analysis. At age 10 days, rats in an obstructed group underwent bilateral ligation and division of the vas deferens, whereas animals assigned to a sham group received a sham operation. At ages 14, 21, 35, 56, 91, and 128 days, rats were sacrificed and blood samples were obtained. Sperm antigens were recognized infrequently and with low intensity by most sera obtained at ages 14 through 56 days. Subsequently, the incidence as well as the intensity of staining of antigens in blots increased at 91- and 128-day intervals in obstructed animals. The increase in antisperm antibodies correlated with the appearance of sperm throughout the epididymis at approximately 56 days postnatally. A set of autoantigens including proteins migrating at 82-78, 76-73, 68, 57, 54, 48, 44, 42, 38-42, 36, and 22 kDa were recognized with the highest frequency and intensity after puberty. A 42-kDa protein appeared to be one of the first autoantigens recognized when obstructed animals underwent sexual maturation. Although individual animals recognized different patterns of sperm autoantigens, a repertoire of 10-12 autoantigens dominated the antisperm antibody response when obstructed animals underwent sexual maturation.
An autoimmune response to sperm occurs after vasectomy, but there is little information on whether similar reactions occur after obstruction of the male reproductive tract at other points. Male Lewis rats received bilateral ligation of the corpus epididymidis or a sham operation at age 10 days, and the subsequent systemic antisperm autoantibody responses were compared to those observed following obstruction of the vas deferens. After sexual maturation, rats with epididymal ligations had antisperm antibodies on an enzyme-linked immunosorbent assay that were significantly higher than those of sham-operated animals and did not differ from antibody levels in vasectomized rats at the same ages. Western blot analysis showed that certain sperm proteins were recognized by antisperm antibodies after both epididymal ligation and vasectomy, including the previously identified "dominant" autoantigens at 73-83, 68-72, 48, 42, and 22 kDa. On the other hand, sera from rats with epididymal ligations recognized 60 and 52 kDa proteins that were not bound by most postvasectomy sera. Conversely, 42-48 and 38-42 kDa bands were more strongly and frequently stained after vasectomy than after epididymal ligation. The results demonstrate that antisperm antibodies are produced after obstruction of the epididymis and that the magnitude of the response is comparable to that after vasal obstruction. Differences in autoantigens recognized after epididymal and vasal obstructions may reflect maturational changes in sperm components that take place during the passage of spermatozoa through the epididymis.