Magnetic Resonance Neurography of the Brachial Plexus Using 3D SHINKEI: Comparative Evaluation with Conventional Magnetic Resonance Sequences for the Visualization of Anatomy and Detection of Nerve Injury at 1.5T.

BACKGROUND AND PURPOSE: This work aims at optimizing and studying the feasibility of imaging the brachial plexus at 1.5T using 3D nerve-SHeath signal increased with INKed rest-tissue RARE imaging (3D SHINKEI) neurography sequence by comparing with routine sequences. MATERIALS AND METHODS: The study was performed on a 1.5T Achieva scanner. It was designed in two parts: (a) Optimization of SHINKEI sequence at 1.5T; and (b) Feasibility study of the optimized SHINKEI sequence for generating clinical quality magnetic resonance neurography images at 1.5T. Simulations and volunteer experiments were conducted to optimize the T2 preparation duration for optimum nerve-muscle contrast at 1.5T. Images from the sequence under study and other routine sequences from 24 patients clinically referred for brachial plexus imaging were scored by a panel of radiologists for diagnostic quality. Injury detection efficacy of these sequences were evaluated against the surgical information available from seven patients. RESULTS: T2 preparation duration of 50 ms gives the best contrast to noise between nerve and muscle. The images of 3D SHINKEI and short-term inversion recovery turbo spin-echo sequences are of similar diagnostic quality but significantly better than diffusion weighted imaging with background signal suppression. In comparison with the surgical findings, 3D SHINKEI has the lowest specificity; however, it had the highest sensitivity and predictive efficacy compared to other routine sequences. CONCLUSION: 3D SHINKEI sequence provides a good nerve-muscle contrast and has high predictive efficacy of nerve injury, indicating that it is a potential screening sequence candidate for brachial plexus scans at 1.5T also.

Cervical corpectomy for resection of ventral intramedullary capillary hemangioma with circumferential involvement of the anterior spinal artery: case report.

There is limited evidence to suggest that anterior approaches for the resection of ventral intramedullary lesions of the cervical spinal cord may result in superior neurological outcomes compared with those following more traditional posterior approaches. To the authors' knowledge, no report of an anterior approach to resect a ventral intramedullary capillary hemangioma exists in the literature. In the following paper, the case of a 75-year-old male who presented with progressive neck and left shoulder pain, weakness of the left hand, myelopathy, and gait imbalance is reported. Postcontrast T1-weighted MRI demonstrated a homogeneously enhancing intramedullary lesion with associated severe impingement of the cervical spinal cord at C-4. Following a C-4 corpectomy, intradural exposure revealed a vascular lesion that circumferentially enveloped the anterior spinal artery. Gross-total resection of the lesion was performed, followed by reconstruction of the corpectomy defect, without neurological deterioration. Pathology was consistent with capillary hemangioma. In this instance, the anterior approach helped to avoid unnecessary neural manipulation and allowed for early identification of normal proximal and distal segments of the anterior spinal artery, which facilitated safe dissection and gross-total removal.

Systemic administration of donepezil attenuates the efficacy of environmental enrichment on neurobehavioral outcome after experimental traumatic brain injury.

BACKGROUND: The acetylcholinesterase inhibitor (AChEI) donepezil (DON) is recommended as a potential treatment for cognition after clinical traumatic brain injury (TBI) and therefore may be prescribed as an adjunct therapy during rehabilitation. However, a dose-response study evaluating DON after a controlled cortical impact (CCI) injury in rats did not reveal cognitive benefits. OBJECTIVE: The aim of this study was to determine the effect of DON on behavioral and histological outcome when combined with environmental enrichment (EE), a preclinical model of neurorehabilitation. It was hypothesized that the combined treatments would produce a synergistic effect yielding improved recovery over neurorehabilitation alone. METHODS: Isoflurane-anesthetized adult male rats received a CCI or sham injury and then were randomly assigned to EE or standard (STD) housing plus systemic injections of DON (0.25 mg/kg) or vehicle (VEH; 1.0 mL/kg saline) once daily for 19 days beginning 24 hr after injury. Function was assessed by established motor and cognitive tests on post-injury days 1-5 and 14-19, respectively. Cortical lesion volume was quantified on day 19. RESULTS: DON was ineffective when administered alone. In contrast, EE conferred significant motor and cognitive benefits, and reduced cortical lesion volume vs. STD (p < 0.05). Combining the therapies weakened the efficacy of rehabilitation as revealed by diminished motor and cognitive recovery in the TBI+EE+DON group vs. the TBI+EE+VEH group (p < 0.05). CONCLUSION: These data replicate previous findings showing that EE is beneficial and DON is ineffective after CCI and add to the literature a novel and unpredicted finding that supports neither the hypothesis nor the use of DON for TBI. Investigation of other AChEIs after CCI injury is necessary to gain further insight into the value of this therapeutic strategy.

Environmental enrichment promotes robust functional and histological benefits in female rats after controlled cortical impact injury.

Environmental enrichment (EE) consistently induces marked benefits in male rats after traumatic brain injury (TBI), but whether similar efficacy extends to females is not well established. Hence, the aim of this study was to reassess the effect of EE on functional and histological outcome in female rats after brain trauma. Twenty-four normal cycling adult female rats underwent verification of estrous stage prior to controlled cortical impact (CCI) or sham injury and then were assigned to EE or standard (STD) housing. Motor function was assessed with beam-balance/beam-walk and rotarod tasks on post-operative days 1-5 and every other day from 1-19, respectively. Spatial learning/memory was evaluated in a Morris water maze on days 14-19. Morphologically intact hippocampal CA(1/3) cells and cortical lesion volume were quantified 3 weeks after injury. No differences were observed between the EE and STD sham groups in any endpoint measure and thus the data were pooled. In the TBI groups, EE improved beam-balance, beam-walk, rotarod, and spatial learning performance vs. STD (p's<0.05). EE also provided significant histological protection as confirmed by increased CA(1/3) cell survival and decreased cortical lesion size vs. STD. These data demonstrate that EE confers robust benefits in female rats after CCI injury, which parallels numerous studies in males and lends further credence for EE as a preclinical model of neurorehabilitation.

Elucidating the role of 5-HT(1A) and 5-HT(7) receptors on 8-OH-DPAT-induced behavioral recovery after experimental traumatic brain injury.

8-OH-DPAT is a 5-HT(1A/7) receptor agonist that enhances behavioral recovery after traumatic brain injury (TBI). This study is a first attempt to decipher whether the benefits induced by 8-OH-DPAT after TBI are mediated by 5-HT(1A) or 5-HT(7) receptors. A single i.p. injection of 8-OH-DPAT (0.5 mg/kg) alone or co-administered with either the 5-HT(1A) or 5-HT(7) receptor antagonists WAY 100635 (0.5 mg/kg) or SB 269970 HCl (2.0 mg/kg), respectively, or vehicle control (1.0 mL/kg) was given 15 min after cortical impact or sham injury. Function was assessed by established motor and cognitive tests. No difference in motor performance was observed among the TBI groups. Spatial acquisition was enhanced, relative to vehicle controls, by 8-OH-DPAT alone and when co-administered with WAY 100635, but not when combined with SB 269970 HCl. These data imply that 5-HT(1A) receptor antagonism does not abate the 8-OH-DPAT-induced cognitive benefits, but 5-HT(7) receptor antagonism does, which suggests that the 8-OH-DPAT-induced benefits in this single administration paradigm may be mediated more by 5-HT(7) versus 5-HT(1A) receptors. Evaluation of a specific 5-HT(7) receptor agonist will further elucidate the contribution of 5-HT(1A) and 5-HT(7) receptors on behavioral recovery conferred by acute 8-OH-DPAT treatment after TBI.

Effects of L-ascorbic acid on two cycles of cisplatin-induced DNA double-strand breaks and phosphorylation of p53 in the liver.

Cisplatin, a commonly used anticancer drug, was studied to investigate its effects on structure, DNA damage and p53 along with the possible protective effects of L-ascorbic acid in the liver. Adult male BALB/c mice were treated with 0, 10 mg/kg L-ascorbic acid and two cycles of cisplatin 1 mg/kg/2.5 mg/kg with or without L-ascorbic acid (17 days recovery period between the cycles) and the livers were collected at 72 h after the last exposure. Structural damage was analyzed in Masson's trichrome and Hortega's silver stained liver tissues. The DNA double-strand breaks with duplex 3' overhangs and 5' P-blunt ends were labeled by in situ oligo ligation by using hairpin oligonucleotide probes. The expression of p53 and phosphorylated p53 (p-p53) was detected by immunohistochemistry. Structural changes such as vacuolization of hepatocytes, pyknosis, infiltration of leukocytes and pericentral fibrosis were observed without any protection from L-ascorbic acid. The reticular fibrous framework was affected and the incidence of Kupffer cells was decreased. Cisplatin induced the DNA double-strand breaks (p<0.001); however, the latter appeared in a p53-independent, but p-p53-dependent manner. L-ascorbic acid showed significant protective effect on cisplatin-induced DNA damage (p<0.001). Cisplatin also enhanced p53 phosphorylation in a dose-dependent manner and L-ascorbic acid reduced this biochemical change only in 1 mg/kg group. In conclusion, cisplatin-induced structural changes are not, but the DNA damage and phosphorylation of p53 are, significantly, but not completely, alleviated by L-ascorbic acid.

Ultrastructural and DNA damaging effects of lead nitrate in the liver.

A ubiquitous environmental toxicant - lead is known to affect several organ systems. This study was designed to investigate the effects of lead nitrate exposure on liver structure and DNA fragmentation. Adult male Wistar rats were treated orally with lead nitrate at the dose levels of 0%, 0.5% and 1% for 60 days and sacrificed on the next day. The liver was processed for thick sections and evaluated after toludine blue staining and by electron microscopy after staining with uranyl acetate and lead citrate. The DNA damage was assessed by DNA fragmentation assay. The liver weight was not significantly affected in the experimental groups. Hepatocyte nuclei were not shrunk, instead lead was mitogenic to hepatocytes as indicated by an increase in the number of binucleated hepatocytes (P<0.05). The number of mitochondria per hepatocyte decreased in a dose-dependent manner (P<0.05). Qualitatively, the necrotic changes such as small to large-sized cytoplasmic vacuoles often displacing the organelles, decrease in hepatocyte microvilli, degeneration of mitochondria, and vacuolar encroachment of nuclei and dilatation of sinusoids were observed. The qualitative changes were induced in a dose-dependent manner. Kupffer cells or Ito cells did not present any notable structural changes. Although the electrophoretic flow of DNA fragments was observed in lead-treated groups, these changes were not significantly different from that in control as evaluated by optical density. In conclusion, lead induces necrotic changes with simultaneous mitogenic activity; however, it does not induce significant DNA damage in the liver.

Can iliac crest reconstruction reduce donor site morbidity?: a study using degradable hydroxyapatite-bioactive glass ceramic composite.

STUDY DESIGN: Prospective study. OBJECTIVE: To prospectively validate the hypothesis that iliac crest donor site morbidity may be a structural issue and by reconstructing the crest its incidence might be reduced. The study also evaluates the efficacy of Chitra hydroxyapatite-bioactive glass ceramic composite (Chitra-HABG) as a material for reconstructing the iliac crest. SUMMARY OF BACKGROUND DATA: Tricortical iliac crest bone graft harvesting is associated with significant donor site morbidity, varying from 3% to 61%. Reconstruction of the defect has been shown to reduce this morbidity, but the only materials which have been shown to be useful and readily available are bioactive apatite-wollastonite glass ceramic and morcellized beta-tricalcium phosphate. METHODS: Twenty-six patients in whom tricortical graft was harvested from the iliac crest and defect reconstructed with an indigenously developed and tested graft substitute-Chitra HABG-were followed up to duration of 1 year. Outcome measures were donor site morbidity as assessed clinically and radiologic assessment for ceramic incorporation, dissolution, fragmentation, and migration. RESULTS: At the end of 1 year from surgery, 25 of the 26 patients (96.15%) had no pain at the donor site, which had been reconstructed. Radiologic evaluation showed that in 21 cases the ceramic incorporation was complete, partial in 3, and absent in 2. Partial dissolution of ceramic was noticed in 3 patients and migration in 1. CONCLUSIONS: This study validates our hypothesis that the donor site morbidity after tricortical iliac crest graft harvesting is probably a structural issue and it can be reduced by reconstruction of the defect. It also highlights the fact that the Chitra-HABG block is an excellent material for reconstruction of the iliac crest defect, as it gets incorporated into the surrounding bone without adverse effects.

l-Ascorbic acid partially protects two cycles of cisplatin chemotherapy-induced testis damage and oligo-astheno-teratospermia in a mouse model.

Cisplatin (cis-diaminedichloroplatinum-II) is a widely used antineoplastic agent in the treatment of a variety of cancers. The aim of the present study was to investigate the testicular toxicity of cisplatin in mice at human therapeutic dose-levels, and to investigate any protective effects of concomitantly administered l-ascorbic acid (i.p.; 10 mg/kg). Adult male BALB/C mice (13-15-week-old) were treated (i.p.) with two cycles of 5 days each of cisplatin with 17 days of recovery period between cycles, as follows: Group I (G-I) - water (N = 10); Group II (G-II) -L-ascorbic acid (N = 6); Group III (G-III) - 1mg/kg (N = 6); Group IV (G-IV) - 1 mg/kg + L-ascorbic acid (N = 6); Group V (G-V) - 2.5 mg/kg (N = 6); and Group VI (G-VI) - 2.5 mg/kg + L-ascorbic acid (N = 8). All animals were sacrificed on third day after the last treatment. The testis weight was decreased in a dose-dependent pattern (G-III - 44% and G-V - 54% against G-I), but l-ascorbic acid (10 mg/kg) recovered the lost weight in G-VI up to 32% against G-V (p<0.05). Seminiferous tubular pathology was indicated by vacuoles, epithelial gaps, epithelial sloughing, delayed spermiation, malorientation of spermatids, germ cell degeneration, phagocytosis of spermatids, multinucleated germ cell formation and atrophy. Structurally abnormal tubules (G-III - 33%; G-V - 100%) were induced, and protective effects were seen in G-IV (77%) and G-VI (25%; p<0.05). The tubular diameter was decreased in G-III-VI, but recovery was seen only in G-IV. The epithelial height was decreased in G-III, G-V and G-VI and the recovery was seen only in G-VI. The sperm count was decreased up to 53% and 71% against control in G-III and G-V, respectively, and recovery up to 47% and 61% was observed in G-IV and G-VI, respectively. The sperm motility was decreased up to 56% and 63% against control in G-III and G-V, respectively, and recovery was only marginal in G-IV and G-VI (p>0.05). Total sperm abnormalities were increased in G-III-V (274%, 156% and 232%, respectively, p<0.05) and l-ascorbic acid protected the effect in G-VI up to 156% (p<0.05). In conclusion, at human therapeutic dose-levels, cisplatin induces testicular damage and spermato-toxicity. l-Ascorbic acid only partially nullifies the gonadotoxic effects of cisplatin.

Ilio-lumbar fixation--the Amrita technique.

STUDY DESIGN: Surgical technique description. OBJECTIVE: To describe a surgical technique of ilio-lumbar fixation with iliac screws, which attempts to overcome some of the current limitations and technical difficulties associated with this surgery. SUMMARY OF BACKGROUND DATA: The iliac screw technique, which is the most commonly used method of ilio-lumbar fixation, has certain limitations that need special consideration. These include soft tissue coverage, improving the strength of distal anchorage, reducing hardware prominence, avoiding complex 3-dimensional rod contouring, preventing neurologic injury, and acetabular violation. MATERIALS AND RESULTS: Over the past 5 years, we have used our technique in 8 patients (4 sacral tumors, 2 fracture dislocations, and 2 spinal tuberculosis). In 6 cases, the sacrum was not available for anchoring and hence was bypassed. The follow-up ranged from 3 to 54 months, and 5 patients had resumed normal activities. In 7 cases, the wound healed primarily and the solitary wound failure was in a previously irradiated skin. Other complications like neurologic deficit secondary to the procedure, acetabular violation, and implant failure were not encountered. CONCLUSIONS: Our technique of ilio-lumbar fixation provides a stable and simple alternative to reconstruct potentially devastating instability of the lumbosacral junction. The 2 iliac screws, when used as described, make the procedure technically easier, reduce the hardware prominence without compromising the stability to construct and provide adequate bone graft.

Hydroxyapatite-bioactive glass ceramic composite as stand-alone graft substitute for posterolateral fusion of lumbar spine: a prospective, matched, and controlled study.

STUDY DESIGN: Prospective, matched, and controlled study. OBJECTIVE: To evaluate the efficacy of hydroxyapatite-bioactive glass ceramic composite (Chitra-HABg) as a stand-alone graft substitute in promoting posterolateral fusion in the lumbar spine as compared with autologous bone. BACKGROUND: The use of ceramics as stand-alone graft substitutes in posterolateral fusion remains controversial. The Chitra-HABg is a new composite that has undergone clinical trials in various orthopedic applications with excellent clinical and radiologic outcomes. METHODS: Twenty-four patients underwent instrumented posterolateral fusion, with Chitra-HABg laid on the left intertransverse bed and autogenous graft on the right side. The primary outcome measure was radiologic consolidation of the graft, and secondary outcome measures were the work status and the Modified Oswestry Disability index. The McNamara and Student chi test were applied for statistical analysis. RESULTS: Although the study was prematurely terminated owing to the high incidence of resorption of Chitra-HABg, 22 of the 24 subjects were followed-up for a minimum of 1 year. At the end of 1-year, excellent radiologic outcome was seen on the right side (autogenous graft) in all the cases, whereas 95% (21/22) of the cases had poor consolidation on the left side (Chitra-HABg). The clinical outcome was rated as good in 16/22 (73%) patients, fair in 5, and poor in only 1 patient, but this had no statistically significant association with the consolidation of the fusion mass. CONCLUSIONS: This study clearly demonstrates that hydroxyapatite-bioactive glass ceramic composites (Chitra-HABg) has no role as stand-alone bone graft substitutes in posterolateral fusion of the lumbar spine, as the composite undergoes resorption without the formation of bridging callus. LEVEL OF EVIDENCE: Level 1.

L-asparaginase production by Streptomyces albidoflavus.

Attempts were made to optimize the cultural conditions for the production of L-asparaginase by Streptomyces albidoflavus under submerged fermentations. Enhanced level of L-asparaginase was found in culture medium supplemented with maltose as carbon source. Yeast extract (2%) was served as good nitrogen source for the production of L-asparaginase. The optimum pH for enzyme production was 7.5 and temperature was 35°C. The release of L-asparaginase from the cells of S. albidoflavus was high when strain was treated with cell disrupting agents like EDTA and lysozyme. The enzyme produced by the strain was purifi ed by ammonium sulfate, Sephadex G-100 and CM-Sephadex C-50 gel fi ltration and the molecular weight was apparently determined as 112 kDa.

Methyl parathion induces the formation of symplasts by round spermatid fusion and alters the biochemical parameters in the testis.

Methyl parathion (MP: O,O-dimethyl-O-4-nitrophenyl phosphorothioate) is an organophosphate pesticide used in agriculture to protect a variety of crops. Food stuffs such as fruits and vegetables could be contaminated with MP, which may be a potential route of exposure. Previous studies have shown that MP is a reproductive toxicant in animal models. The present study was designed to investigate the mechanism of symplast formation and biochemical changes that occur in the testis, following MP exposure. MP was treated to adult male Wistar rats (N=5/dose/sample time) as follows. Experiment 1 - 0, 0.75 or 1.5mg/kg/d i.p. for 25 days and experiment 2 - 0 or 3.5mg/kg/d p.o. for 25 days and sacrificed on Day 17, after the last exposure. Light microscopic examination of testis was made to evaluate the structural changes and also to establish a process of symplast formation and destruction. Quantitative biochemical estimations were made in the testis for acid phosphatase (ACP), cholesterol, total protein, uric acid, and lactate dehydrogenase (LDH). MP induced structural changes in the testis in consensus with the previous studies. The symplasts were found in the testes in experiment 1. Those cells were formed due to the cell fusion of round spermatids. The symplasts were degenerated by nuclear fragmentation. The nuclear fragments were extruded from the symplasts leaving behind only the eosinophilic cytoplasm. The cell fusion and multinucleated giant cell formation was the reason for MP induced tubular atrophy. Number of tubules with symplasts increased in experiment 1 in a dose-dependent pattern. Johnsen's scores also decreased in a dose-dependent manner in experiment 1 indicating a dose-dependent tubular destruction. The ACP, cholesterol, total protein, and LDH levels decreased in both experiments against their respective controls, whereas the uric acid level decreased in experiment 1 and increased in experiment 2 (P<0.01-0.001). The effects in experiment 1 were dose-dependent. In conclusion, MP induces the formation of symplasts by cell fusion of round spermatids, which is a process involved in tubular atrophy and also induces biochemical changes in the testis.

The effect of carbamazepine on sperm counts in Wistar rats--reflecting upon its mitogenic potential.

The present study was aimed to investigate the effects of carbamazepine, an antiepileptic drug, on sperm count in rats. Male Wistar rats were treated with carbamazepine at doses of 9, 18, and 36 mg/kg for five consecutive days. Following the last exposure, on days 14 and 35, spermatozoa were collected from epididymis and counted. On day 14, carbamazepine treatment decreased the sperm number in a dose dependent pattern. On day 35, 9 mg/kg and 36 mg/kg of carbamazepine increased the sperm number in comparison with untreated rats. The results of the study suggest that carbamazepine is a germ cell mitogen.

Incidence, types and clinical implications of a non-metrical variant--mylohyoid bridging in human mandibles.

Mylohyoid bridging (MB) is a non-metrical variant of the human mandible. The incidence and types of MB were investigated in 264 mandibles (edentulous 116, semi-dentulous 90 and dentulous 58). No mandible showed a complete type of MB, although 19 (7.2%) mandibles had a partial type. These were classified into two subtypes: distal partial (DP; Type I) and proximal partial (PP; Type II), depending on their location over the mylohyoid groove. The MB was present unilaterally in 7.76% of edentulous mandibles: right side 5.17% (3.45% PP type and 1.72% DP type) and left side 2.59% (1.72% PP type and 0.86% DP type). Of the semi-dentulous mandibles 3.33% had DP type of MB, 1.11% on the right side and 2.22% on the left side, and of the dentulous mandibles 1.72% had DP type of MB on the right side. A total of 13 mandibles out of 264 (4.92%) had unilateral MB. No dentulous mandible had bilateral MB, but 3.45% of edentulous and 2.22% of semi-dentulous mandibles did have. In total, 6 mandibles out of 264 bones (2.27%) had bilateral MB. Of the bilateral incidences 1.72% of edentulous mandibles had a DP-DP combination and the remaining 1.72% had a PP-DP combination. However, both instances of bilateral MB in semi-dentulous mandibles were of PP-DP combination. The incidence or types of MB showed no statistically significant differences between the groups or sides (p > 0.5; chi(2) test). In conclusion, the complete type of MB is a rare occurrence. The incidence increases with age, as edentulous mandibles had a higher incidence of MB than the other two groups. Clinically, MB may compress the mylohyoid neurovascular bundle, leading to neurological or vascular disorders.

The effects of carbamazepine on sperm morphology in wistar rats.

UNLABELLED: Carbamazepine (5 H-dibenz (b, f) azepine-5-carboxamide), is an antiepileptic drug which is expected to be administered regularly over a substantial part of patients lifetime. As the gender focus in epilepsy the later years has primarily been on women, there certainly is a lack of studies focused on the effects particular to men. The present study was aimed to investigate its effects on germ cell's by employing the sperm morphology assay. Twelve groups of male wistar rats were treated with sterile water 0.5 ml, cyclophosphamide (CP) 20 mg/kg, carbamazepine 9, 18, 36 mg/kg (i.p) and 2% gumacasia 0.25 ml/100 g respectively for 5 consecutive days at intervals of 24 hrs. Following the last exposure, on days 14 and 35 sperm morphology assay was conducted as per the standard procedure. Mann-Whitney 'U' test was used for statistical analysis and the level of significance was P<0.01. Neither carbamazepine nor cyclophosphamide induced formation of abnormally shaped sperms at 14 day time interval. Whereas on day 35, with 18 mg/kg dose level of carbamazepine there was an increase in the number of sperms with heads defects (P<0.01); Whereas in the other two dose levels the number of abnormally shaped sperms had decreased. 2% gumacasia increased the number of sperms with tail defects at day 35. (Mann-Whitney 'U' test). CONCLUSION: Carbamazepine and 2% gumacasia could be germ cell mutagens and could cause infertility on prolonged use therefore further studies with serum drug level estimations are needed.

The reproductive toxicity of the organophosphate pesticide 0, 0-dimethyl 0-4-nitrophenyl phosphorothioate (methyl parathion) in the male rat.

Methyl parathion (MP) is a pesticide widely used to protect crops but also illegally used in many countries for spraying homes and businesses to contain insects. The present study was planned to investigate the effects of MP on the male reproductive organs in the rat. Male Wistar rats (13-14 weeks old) were treated with MP and sacrificed as follows. Experiment 1:0 (water vehicle), 1.75, 3.5 or 7 mg/kg (i.p.) for 5 days and sacrificed on day 14; experiment 2:0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 130; experiment 3: 0, 0.5 or 1 mg/kg (i.p.) for 12 days and sacrificed on day 77; experiment 4: 0, 0.75 or 1.5 mg/kg (i.p.) for 25 days and sacrificed on day 17; experiment 5: 0 or 3.5 mg/kg (p.o.) for 25 days and sacrificed on day 17 after the last exposure. The reproductive organs were removed, weighed and processed for histopathological analysis. Structural changes, for example the morphology of the epithelium and the lumina of the organs, were observed in all animals. Biochemical estimates of acid phosphatase (ACP), cholesterol, total protein, uric acid, and vitamin C were conducted in the epididymes. The weight of the epididymes increased in experiment 2 in a dose-dependent pattern (p < 0.01) and decreased in experiments 4 and 5 (p < 0.01). The weight of the ductus deferens decreased in experiment 3 at 1 mg/kg dose level (p < 0.001) and increased in experiment 5 (p < 0.05). The weight of the seminal vesicle decreased in experiment 3 at both 0.5 mg/kg and 1 mg/kg dose levels (p < 0.001), and increased in experiment 5 (p < 0.01). The weight of the prostate decreased in experiments 4 (in a dose-dependent pattern) and 5 (p < 0.001). ACP levels decreased in experiment 4 (p < 0.001) with a greater effect at 0.5 mg/kg than at 1 mg/kg. In experiment 5 (p < 0.01) cholesterol levels decreased to less than 50% of the control level for this experiment (p < 0.01) and protein levels also decreased (p < 0.01). Vitamin C levels decreased in a dose-dependent pattern in experiments 4 (p < 0.001) and 5 (p < 0.01). There were no effects on uric acid level. Sperm density was decreased in the epididymes of the rats treated and the epithelium of the epididymis and ductus deferens showed cellular necrosis, brush-border disruption and nuclear pyknosis. Nuclei were haloed, except in experiment 2 and the 0.5 mg/kg group of experiment 3. Methyl parathion did not induce significant changes in the structure of the seminal vesicle and prostate, except that epithelial folding was shorter than in the control. In conclusion, MP is a reproductive toxicant in the male rat and causes deterioration in the structural integrity of the reproductive organs and also the biochemical parameters in the epididymis.

Dacarbazine induces genotoxic and cytotoxic germ cell damage with concomitant decrease in testosterone and increase in lactate dehydrogenase concentration in the testis.

Treatment of cancers with cytotoxic agents such as alkylating drugs often, but not always results in transient to permanent testicular dysfunction. The present study was planned to investigate the effects of dacarbazine [5-(3,3-dimethyltriazeno) imidazole-4-carboxamide] on testicular function in mice. Swiss albino mice (9-12 weeks old) were treated with 0, 5, 25, 50, or 100mg/kg body weight/day dacarbazine (i.p.) for 5 days at intervals of 24h between treatments. Mice were sacrificed on days 7, 14, 21, 28, 35, 49, and 70 after the last treatment (6 mice/dose/sample time), and the epididymal sperm count, sperm motility, sperm morphology, testicular histopathology (qualitative histopathology, seminiferous tubular diameter and epithelial height), and intra-testicular levels of testosterone and lactate dehydrogenase were assessed. Dacarbazine decreased the body weight only on day 28 at 25mg/kg dose-level, but increased the paired testes weights at 50mg/kg on day 7, at 25-100mg/kg on day 14, and at 25 and 50mg/kg on day 21 (P<0.05-0.01; one-way ANOVA and Bonferroni's post hoc test). The sperm count was decreased on all sampling days except at 5 and 25mg/kg dose-levels on day 70, but with severe oligospermia on days 28 and 35 (P<0.05-0.001). The sperm motility was decreased at 100mg/kg on days 14 and 21, at 5, 25, and 100mg/kg on day 28, and at all dose-levels on day 35 (P<0.05-0.001). Dacarbazine induced both head and tail abnormalities and some sperms with cytoplasmic droplets, but significant increase was seen in all dose groups on days 14 and 21, and at 100mg/kg dose-level on day 35. Drug-induced epithelial sloughing was seen on days 14-35 and other histopathological changes observed were vacuoles and abnormal cells. The STD was increased at 25-100mg/kg on day 7, at all dose-levels on day 14, at 50-100mg/kg on days 21 and 28, but without any effects on days 35-70 (P<0.05-0.001), and the tubular lumen was found dilated. The SE was increased on days 7, 21 and 28 at 100mg/kg and on day 14 at 50-100mg/kg. Dacarbazine reduced the intra-testicular testosterone level at 100mg/kg on day 7, at 5, 50 and 100mg/kg on day 14, at all dose-levels on days 21, 28, and 35, and at 50mg/kg on day 49 (P<0.05-0.001). The intra-testicular lactate dehydrogenase concentration increased at all dose-levels up to day 35, but without any effect on days 49 and 70 (P<0.05-0.001). There was no particular dose-response of dacarbazine on any parameters tested. The sperm count (except on day 7-positive correlation; Pearson product moment correlation) or sperm motility did not have any relation but increase in abnormal sperms showed negative correlation with decrease in testosterone level on days 7, 21 and 28. Decrease in sperm count was in negative correlation on days 14 and 35, and increase in abnormal sperms showed positive correlation on day 35 with increase in LDH level. Finally, the decrease in sperm motility had no correlation with increase in abnormal sperm shapes. We conclude that dacarbazine is genotoxic and cytotoxic to the mouse testis in a transient fashion, and these effects are exerted along with decrease in testosterone and increase in lactate dehydrogenase levels in the testis.

Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat.

The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat.

Neonatal methyl parathion exposure affects the growth and functions of the male reproductive system in the adult rat.

Methyl parathion (MP) is a well-known organophosphorus pesticide, to which humans are exposed in fruit and vegetables as residues of 0-2 mg/kg, children being at higher risk of exposure. The present study was planned to investigate the effects on the adult male reproductive functions of MP following neonatal exposure. New born male Wistar rat pups were treated orally with either 0 or 0.5 mg/kg MP from postnatal day (PND) 3 to PND 28 and sacrificed on PND 98 for the purpose of examination of the reproductive system. Methyl parathion lowered the body weights from days 10 to 24 (p < 0.01), the weights of the reproductive organs (p < 0.05-0.01), the epididymal sperm count (p < 0.01) and the homogenisation-resistant testicular spermatid head count (p < 0.01) and also decreased acid phosphatase (ACP), cholesterol, uric acid, protein, ascorbic acid, and lactate dehydrogenase (p < 0.01) levels in the testis but only ACP and cholesterol in the epididymis. The levels of abnormal sperm and testosterone in the testis were increased (p < 0.01), whereas the leutinising hormone level and total number of seminiferous tubules decreased in the testes of treated rats (p < 0.01). A few tubules showed exfoliation of epithelium and vacuoles. The incidence of stage XIV tubules and ratios of meiotic figures and elongating spermatids to Sertoli cell nucleoli decreased (p < 0.01; Mann-Whitney U test). The present results indicate that MP acts as an endocrine disruptor and consequently affects the postnatal development and growth of the male reproductive organs in the rat. These findings are important to the general public, as there is a chance of children being exposed to this pesticide.