The effect of the female rat estral cycle on microsomal drug metabolism in-vivo and in-vitro has been studied. Two microsomal enzymes, aminopyrine-N-demethylase and aniline hydroxylase showed a greater specific activity (p less than 0.01) in the diestrus phase of the estral cycle while the oxidative enzyme aryl hydrocarbon hydroxylase and the conjugative enzyme, glucuronyl transferase, were not affected. In vivo studies which included theophylline and antipyrine metabolism, and hexobarbital sleeping times showed no difference between the different phases of the estral cycle. Conflicting evidence about the effect of steroid sex hormones on hepatic drug metabolism is discussed.

Animals↗

PubMedDate not supplied

Dietary restriction modifies fever response in aging rats.

Intermittent (every-other-day) feeding initiated at 19 months of age and continued for 12 weeks, led to a moderate decrease in body weight of aging rats, enhanced survival and modified diurnal changes in body temperature and fever response to bacterial endotoxin (E. coli lipopolysaccharide, LPS). Diet-restricted animals which survived LPS administration, displayed reduced febrile response, i.e. (i) a moderate hypothermia in an early phase, and (ii) a delayed onset of body temperature elevation, as compared with their ad libitum-fed controls. However, peak body temperature values were similar in both groups. The rats of both groups which did not develop hyperthermia in response to LPS, died within 24 h of LPS administration. In control, but not in diet-restricted rats, variations in body weight during the 12 weeks prior LPS administration may be predictable in regard to their survival after LPS treatment. It seems that the resistance to bacterial endotoxin in aging rats is associated with their ability to develop hyperthermia.

Journal Article↗

PubMedDate not supplied

Suppression and recovery of spermatogenesis in dibromochloropropane treated rats.

Fertile male rats were injected subcutaneously with DBCP dissolved in DMSO at a dose of 20 mg DBCP/kg BW once a week for three consecutive weeks. One testis was removed 3-7 weeks after the last injection. Following standard histological procedure the percentage of damaged seminiferous tubules was determined. Damage to various degrees was noted in 70% of the injected animals. No damage was evident in the control animals injected with the solvent alone. The second testis was removed about 27 weeks later. In about 70% of the animals showing damage in the first testis recovery was evident with presence of active spermatogenesis as revealed in histological sections. There was some loss of body weight during the DBCP injection period compared with controls. However, with time these differences disappeared. At sacrifice, testis, liver and kidneys weights were reduced in the DBCP treated animals as compared with the controls. Testicular weight was negatively correlated with the degree of observed testicular damage but not correlated with the degree of testicular recovery.

Animals↗

PubMedDate not supplied

Testicular damage development in rats injected with dibromochloropropane (DBCP).

Dibromochloropropane (DBCP) is an effective nematocide which was shown to suppress spermatogenesis and cause infertility in men and rats exposed to the compound. These damages were described only after 6-8 weeks post injection. The present study was set to detect the early development of the testicular damages. Rats were injected s.c. with DBCP 50 mg/kg. Control animals were injected with the vehicle alone (DMSO). Groups of animals were sacrificed 24 h, 1, 2, 3 and 4 weeks post injection. Body weight of DBCP treated animals was reduced from the second week post injection. Organs' weights of the DBCP treated rats, corrected for differences in body weights, were similar to those of controls. Four weeks post injection testes and accessory gland weights were significantly reduced as compared with controls. Percentage of damaged tubules in the DBCP treated animals were elevated from 16.6 +/- 3.5 at the first day to 70.2 +/- 6.4 at the 4th weeks. Concomitantly with the advance of tubular damage was a reduction in epididymal sperm count in the DBCP treated rats. One week post injection histological changes were evident. These included multinucleated giant cells and tubules blocked with sperm granuloma. It seems that alterations of spermatogenesis appear earlyer and are already noticeable one week post injection.

Animals↗

PubMedDate not supplied

The effect of dibromochloropropane (DBCP) on in vitro cyclic AMP levels and testosterone production in rat testes.

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg BW. Animals were sacrified 20 weeks after last injection. Body and testes weights were recorded and testes were taken for standard histological preparation and for in vitro experiments. The in vitro experiments were carried out on testes slices (90-110 mg) incubated for 3 h with or without the addition of hCG to the incubation medium. Cyclic AMP content of the tissue as well as testosterone released into the incubation medium were determined. Testes weights of DBCP treated animals were 68% lower than that of controls. All semiferous tubules were damaged and shrunken, thus, their number per microscope field was 2.6 times that of controls. Cyclic AMP levels in testes slices were similar in both DBCP treated and controls. The addition of hCG stimulated cyclic AMP accumulation to a much higher level in the DBCP treated than in controls. When calculated per one pair of testes the content in unstimulated pair was more than twice that of DBCP treated. Stimulation of hCG increased both DBCP treated and controls to similar levels. Testosterone release into the medium by slices was higher in DBCP treated than in controls and so was also the increment due to hCG stimulation. Similar results were obtained when testosterone release was calculated per one pair of testes. It is suggested that since the major testicular compartment damaged by DBCP is the tubular one, the proportion of the interstitium per testicular unit weight is larger than in controls, thus, cyclic AMP content increment due to hCG stimulation is much higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Long term effects of dibromochloropropane (DBCP) on male rats' reproductive system.

Adult male rats were injected s.c. once a week for 3 weeks with DBCP, 20 mg/kg B.W. Animals were sacrificed 5, 9, 13, 17, 25 and 50 weeks after last injection. Body weight was recorded once a week. Prior to sacrifice each male was presented with proestral females in order to determine the male's mating behaviour and fertility. Testes were removed, weighed and taken for standard histological examination. DBCP treatment caused a reduction of body weight which reverted back to control levels some 17 weeks post injection. Testes weights were reduced and remained low despite the recovery of body weight. Generally, all males showed normal mating behaviour but most of them were infertile. Testicular histology showed a correlation between decreasing testicular weight and increasing percentage of degenerated seminiferous tubules, which was on the other hand correlated with decreasing tubular diameter. Serum levels of FSH and LH were significantly increased in the infertile DBCP treated males while values for the fertile ones were similar to those of controls. There were no differences in serum testosterone levels between DBCP treated and control animals. It is concluded that in DBCP treated rats testicular degenerative damages are associated with increased circulating gonadotrophin levels and with normal testosterone levels. Although mating behaviour is unaffected fertility is depressed and does not recover for at least 50 weeks post injection. It is suggested that DBCP treatment affects mainly the activity of the Sertoli cells while the Leydig cells are affected to a much lesser degree.

Animals↗

PubMedDate not supplied

Ultrastructure of testicular cells in rats treated with dibromochloropropane (DBCP).

Three days after a single injection of rats with dibromochloropropane (DBCP) the testicular seminiferous tubules displayed focal damage, which became more pronounced six days after the treatment. Severely damaged tubules exhibited an almost complete exfoliation of the germ cells, while the Sertoli cells' lining remained mostly intact. The most affected germ cells were the spermatids. The mitochondrial sheath of the midpiece was often incomplete, vacuolated and/or broken into several pieces. In many cases the mitochondrial sheath protruded towards the interior, thus partially separating dense fibers 1, 2 and 9 from 3 to 8. In addition, cross sections revealed several midpieces of different flagellae surrounded by a single plasmalemma. In young spermatids, an atypical acrosome formation was noted concomitantly with a progressive emptying of the central nuclear region. This resulted in nuclei with electron lucent center surrounded by a chromatin belt. Sertoli cells displayed intense phagocytotic activity, their cytoplasm containing increased numbers of lysosomes, cellular debris and axonemal fragments.

Administration, Cutaneous↗

PubMedDate not supplied

Age-dependent differences in the effects of 1,2-dibromo-3-chloropropane (DBCP) on fertility, sperm count, testicular histology and hormonal profile in rats.

This study was set up to determine if there are any age-dependent differences in the adverse effects of DBCP on the reproductive system of male rats. Groups of male rats were injected at the ages of 7,30 or 90 days with a single (50 mg kg-1 body weight) or repeated (20 mg kg-1 body weight once a week for 3 weeks) dose of DBCP, dissolved in DMSO. Ninety days after the last injection the males' fertility was estimated and the animals were killed. Blood was collected for future hormone assays, organs were weighed, testes were then taken for histological studies and sperm counts. The results were compared with those of control peers. The results showed that animals injected at the ages of 7 or 90 days under both regimens of treatment were adversely affected. The damage was noted in their fertility rate, sperm production, testicular histology and hormonal profile. Those injected at the age of 30 days showed only an insignificant variation compared with controls.

Age Factors↗

PubMedDate not supplied

The effects of 1,2-dibromo-3-chloropropane (DBCP) on general toxicity and gonadotoxicity in rats.

This study was set to determine if there is a correlation between the general toxic effect and the gonadotoxic effect of DBCP on male rats. Groups of male rats were injected with a single dose of DBCP (50 mg kg-1) dissolved in dimethylsulfoxide (DMSO). Twenty four hours, one and four weeks post injection animals were sacrificed. Blood was collected for enzymes' and hormones' assays. Organs were weighed and testes were taken for histological examination and sperm counts. The results showed that DBCP at a dose of 50 mg kg-1 had a general toxic effect expressed by reduction in body and liver weights and reduced activities of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). These changes show a tendency to revert to normal values with time. On the other hand, gonadotoxic effects increase in severity with time. The weight of testes and epididymides were reduced, sperm counts decreased and histological damage advanced, and FSH and LH blood levels increased 4 weeks post injection. It seems that in rats the gonadotoxic effect of DBCP is dissociated from the general toxic effects.

Alanine Transaminase↗

PubMedDate not supplied

Age-related changes of postural control: effect of cognitive tasks.

BACKGROUND: Postural control and falls in the elderly constitute a major health problem. The interest in balance deficits is growing, as concern about the rising costs of health care increases. This issue is particularly relevant to the elderly population in which falls occur most frequently. Postural control in the elderly was studied using a cognitive approach. OBJECTIVE: The purpose of this study was to study the characteristics of central processing of postural control while performing cognitive tasks. METHODS: A dual-task procedure was developed to estimate the level of automaticity of a quiet upright standing task. The effect of a concurrent attention-demanding task (modified Stroop test) on the efficiency of balance control in the elderly was determined using force platform and electromyography measurements. RESULTS: It was found that there is an increase in postural sway in old subjects compared with young subjects when performing single tasks and dual-task tests. The results of the study demonstrate that postural adjustments require cognitive processing; young and old subjects showed similar interference effects on postural steadiness (postural sway) caused by the concurrent attention-demanding task. The results are corroborated by the hypothesis that a dual task gives information on the restoration of automaticity of postural control in old age by a central reorganization process. When performing a dual task tested on a narrow base of support, the old subjects decreased their body sway, while the younger did not. According to electromyography measurements, the older subjects increased their muscle activity in the tibialis anterior and soleus muscles, using slow-twitch motor units compared with the younger subjects. CONCLUSIONS: Both alterations (cognitive and base of support) have a substantially greater effect on the elderly than on the young. The older subjects decreased their body sway by activating a cocontraction strategy of postural control around the ankle joint, probably because of the danger to their postural stability.

Adult↗

PubMedDate not supplied

Effects of regular walking on postural stability in the elderly.

BACKGROUND: Both age and lack of physical activity may be responsible for poor health and poor balance control. Conversely, physical activity may modulate postural control in elderly people. OBJECTIVE: An observational study was performed in older adults to explore whether walking on a regular basis might prove to be beneficial not only to the cardiovascular system but also to maintaining a good balance. METHODS: Twenty-two healthy older subjects walking on a regular basis (DW group) and 121 healthy control older subjects who did not walk regularly (NW group) were studied. The subjects included in the study were free from major gait and postural disorders. An instrumented force platform was used to measure the time-varying displacements of the center of pressure under eight static conditions and postural limit tests. An isometric test was performed to evaluate lower limb muscle strength, and a static two-point discrimination test evaluated the innervation density of the slowly adapting receptors of the sole of the first toe. RESULTS: The DW group had a significantly better (p < 0.05) postural stability under static conditions than the NW group. There were no significant differences in postural limit tests and in two-point discrimination between the groups. The DW group had significantly higher values of ankle plantar flexor and knee extensor strengths, while there were no significant differences in ankle dorsiflexors and knee flexors. None of the DW group reported experiencing a fall during the previous 6 months compared with 16% in the NW group who reported at least two falls during the last half year. CONCLUSIONS: Walking on a regular basis in old age may have the potential to modulate stability. It was found that healthy older subjects, who walked on a regular basis since their retirement, have better postural control, especially in their static balance, than those who do not. The laboratory results were accompanied by the important finding that although older subjects who walk on a regular basis walked much more than nonwalkers, they did not suffer from falls.

Accidental Falls↗

PubMedDate not supplied

Effect of central early postnatal 6-hydroxydopamine administration on brain catecholamines and pituitary-adrenal function in adulthood.

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Adrenal Glands↗

PubMedDate not supplied

Reproductive performance of dibromochloropropane-treated female rats.

Dibromochloropropane (DBCP) is an effective nematocide which has been shown to suppress spermatogenesis and cause infertility in both men and male rats. There are no similar reports concerning the effects of DBCP on female reproduction. The purpose of the present study was to attempt to interfere with the various phases of oogenesis. Proestral or pregnant rats were injected subcutaneously once with 40 mg/kg DBCP on one of each days of L12-L20 of gestation; a double dose (80 mg/kg) was injected in eight consecutive days (L11-L18). In addition, L13 fetuses were injected--directly into the amniotic sac--with 0.1 mg DBCP. Pooled data from the various days of gestation revealed that postimplantation losses were three times as high in the DBCP-treated animals as in DMSO-treated controls. Perinatal deaths were 58% higher and mean pup weights were 30% lower in the DBCP-treated rats than in controls. The reproductive performance of females exposed to DBCP while in utero was affected only to a limited degree (reduced number of ovulations and implantations) as compared with their DMSO counterparts. Doubling the dose (80 mg/kg) seriously reduced the birth weight of pups (50% of controls), all of which died within several hours post-partum. Direct injection of DBCP into embryos or to proestral rats did not have any adverse effects on their future reproductive performance. In contrast to the effect on spermatogenesis, it appears that oogenesis and ova are unaffected by DBCP.

Animals↗