Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

Prostatic and testicular parameters in lepromatous patients.

OBJECTIVES: To evaluate PSA (Prostate-specific antigen) parameters in patients with lepromatous leprosy (LL). DESIGN: In a retrospective study, 23 male patients with LL were evaluated. PSA parameters (serum total PSA (tPSA), free PSA (fPSA), free-to-total PSA ratio (f/tPSA), PSA Density (PSAD)) were assessed. PSA parameters were compared with a control group. RESULTS: The mean tPSA, fPSA, f/tPSA, prostate volume, and PSAD values of the patient group with LL were 1.87 +/- 0.81 ng/ml, 0.67 +/- 0.29 ng/ml, 0.36 +/- 0.11, 41.08 +/- 23.65 ml and 0.055 +/- 0.037, respectively. The mean tPSA, fPSA, f/tPSA, prostate volume, and PSAD values of the control group were 2.71 +/- 0.91 ng/ml, 0.80 +/- 0.34 ng/ml, 0.30 +/- 0.08, 65.0 +/- 28.73 ml and 0.049 +/- 0.028, respectively. The mean tPSA and prostate volume values were found to be significantly lower in the patient group with LL (p = 0.002 and 0.004, respectively). No significant difference was found between two groups in terms of mean fPSA and PSAD values (p = 0.18 and 0.5, respectively). The mean f/tPSA value was found to be significantly higher in the patient group with LL (p = 0.02). Testes in 16 (69%) patients with LL were bilaterally atrophic. CONCLUSIONS: Serum tPSA values and prostate volumes in the patients with LL were significantly reduced and f/tPSA values were significantly increased. Testicular atrophy in the lepromatous cases might be due to leprosy-related orchitis and associated with a reduction in prostatic volume.

Toxicological assessment of Ricinus communis Linn root extracts.

Ricinus communis Linn (Euphorbiaceae) plant parts are claimed to be used as carminative, asthma, bronchitis, leprosy, anti-inflammatory, cathartic, and aphrodisiac. The toxicological study was carried out in the root part of the plant. The collected root was extracted with methanol and water. The extracts were vacuum-dried to yield the respective aqueous (AE) and methanol (ME) extracts. Toxicological assessment sought to determine the safety of Ricinus communis root extracts. The extracts were evaluated in the acute toxicity study (OECD-423 guidelines) and 90 days repeated dose toxicological assessment in Wistar albino rats. The acute oral toxicity of the aqueous (AE) and methanol (ME) extracts did not produce any toxic symptoms or mortality at the dose level of 2000 mg/kg in rats. In the 90 days (sub-chronic toxicity) repeated dose toxicity study the extracts (AE and ME) were administered 1000 mg/kg daily through oral route. The sub-chronic toxicity study demonstrated no significant changes in body weight, food, and water intake. Hematology parameters RBC, WBC, DLC, Hb, blood clotting time, and the biochemical parameters glucose, blood urea nitrogen, creatinine, total cholesterol, total protein, total bilirubin AST, ALT, and ALP were estimated. Histopathology observation of the major vital organs (liver, kidney, heart, spleen, lungs, ovary, testis, and brain) were tested. The hematology, biochemical and histopathology evaluations did not show any adverse effects in any of the organs tested. These results demonstrate the non-toxic nature of the root extracts AE and ME can be used for long-term usage in clinical practice.

Measurement of testicular volume in smaller testes: how accurate is the conventional orchidometer?

The aim of this study was to evaluate the accuracy of different methods, including the Seager orchidometer (SO) and ultrasonography (US), for assessing testicular volume of smaller testes (testes volume less than 18 mL). Moreover, the equations used for the calculations--the Hansen formula (length [L] x width [W](2) x 0.52, equation A), the prolate ellipsoid formula (L x W x height [H] x 0.52, equation B), and the Lambert equation (L x W x H x 0.71, equation C)--were also examined and compared with the gold standard testicular volume obtained by water displacement (Archimedes principle). In this study, 30 testes from 15 men, mean age 75.3 (+/-8.3) years, were included. They all had advanced prostate cancer and were admitted for orchiectomy. Before the procedure, all the testes were assessed using SO and US. The dimensions were then input into each equation to obtain the volume estimates. The testicular volume by water displacement was 8.1 +/- 3.5 mL. Correlation coefficients (R(2)) of the 2 different methods (SO, US) to the gold standard were 0.70 and 0.85, respectively. The calculated testicular volumes were 9.2 +/- 3.9 mL (measured by SO, equation A), 11.9 +/- 5.2 mL (measured by SO, equation C), 7.3 +/- 4.2 mL (measured by US, equation A), 6.5 +/- 3.3 mL (measured by US, equation B) and 8.9 +/- 4.5 mL (measured by US, equation C). Only the mean size measured by US and volume calculated with the Hansen equation (equation A) and the mean size measured by US and volume calculated with the Lambert equation (equation C) showed no significant differences when compared with the volumes estimated by water displacement (mean difference 0.81 mL, P = .053, and 0.81 mL, P = .056, respectively). Based on our measurements, we categorized testicular volume by different cutoff values (7.0 mL, 7.5 mL, 8.0 mL, and 8.5 mL) to calculate a new constant for use in the Hansen equation. The new constant was 0.59. We then reexamined the equations using the new 0.59 constant, and found that the equation Volume (V) = L x W(2) x 0.59 was the best for describing testicular volume among our subjects (difference between the new equation and the gold standard of water displacement = 0.19 mL, P = .726). We also found that US was more precise in measuring testicular dimensions. We propose a new formula, V = L x W(2) x 0.59, to assess the volumes of smaller testes.

Cytology of testicular changes in leprosy.

OBJECTIVE: To study the changes in testicular aspirates and semen of patients with leprosy. STUDY DESIGN: A prospective study of 56 patients in the reproductive-age group, with no record of treatment for leprosy. Both Ridley-Jopling and WHO classification systems were used. Skin and/or nerve biopsies were performed for documentation of the diagnosis. Semen analysis and fine needle aspirates of the testes were performed. Smears from the testicular aspirates were stained with May-Grünwald-Giemsa and Ziehl-Neelsen stain. RESULTS: Five patients were unable to produce an ejaculate. Abnormal semen analysis and/or testicular aspirates were seen in 24 (42.8%) patients. Eleven had oligospermia and eight azoospermia. Abnormalities in testicular aspirates ranged from hypospermatogenesis (4) through maturation arrest (1) and atrophy (11). Two patients had hydrocoele, and two had associated microfilariae. Three patients with multibacillary leprosy had type 2 reaction. Mycobacterium lepre was demonstrable in testicular aspirates from all patients with multibacillary and in three with paucibacillary leprosy. CONCLUSION: Abnormal semen analysis and/or testicular aspirates occur in a very high percentage of patients with leprosy. While this is expected for multibacillary disease, the high incidence in the paucibacillary form was surprising. With the rapid elimination of leprosy, fertility-related disability might emerge as a major problem in these people.

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Osteoporosis due to testicular atrophy in male leprosy patients.

A study was conducted to examine the relationship of testicular atrophy to bone metabolism in male leprosy patients. The study consisted of 31 leprosy patients (mean age: 62.0 years) and 31 healthy control men (mean age: 60.0 years). Measurements were made of their serum levels of free testosterone (FT), estradiol (E2), luteinizing hormone (LH) and 25-hydroxyvitamin D (25 OHD). Bone mineral density (BMD) was measured at radial sites and the lumbar vertebral bodies (L2-L4) by dual-energy X-ray absorptiometry using a Hologic QDR-2000 densitometer. FT and E2 levels were significantly lower and LH levels higher in leprosy patients than in controls. This represents a primary hypogonadal pattern. A value of 7.20 pg/ml of FT ( = Mean - 1 SD of control) was used as a cut off value, and the subjects were subdivided into a hypogonadal group (HG) and a non hypogonadal group (non-HG). When the subjects were compared for differences in age, age at onset of disease, duration of disease, body mass index and BMD, only the duration of disease and BMD were significantly different between the two groups. Furthermore, BMD of the forearm significantly correlated with FT levels (r = 0.689, P < 0.0001). Low BMD may be due to orchitis and testicular atrophy.

Síndrome da sulfona e reaçäo reversa / Sulfone syndrome and reverse reaction

Um homem de 68 anos de idade, cor preta, interna-se por hanseníase multibacilar, nao tratada, apresentando infiltraçao cutânea difusa e nódulos raros de Eritema nodoso hansênico. Na época, (1982) foi tratado com sulfona e talidomida. Um mês e meio após o início do tratamento surge erupçao cutânea eritematosa difusa, acompanhada de febre alta, adenomegalia generalizada e hepatoesplenomegalia. O hemograma demonstrou leucocitose intensa com linfocitose e atipias de linfócitos. Evoluiu com icterícia, desidrataçao, confusao mental, falecendo no 4( dia após instalaçao da erupçao referida. Na necrópsia o substrato do exantema generalizado é um infiltrado linfocitário pleiomórfico em pele, mucosas e vísceras. Este quadro foi interpretado como a "Síndrome da Sulfona", manifestaçao de hipersensibilidade à esta droga e que em muitos aspectos mimetiza ou induz o aparecimento de uma monucleose infecciosa. Há algumas publicaçoes sobre esta síndrome, algumas relatando casos fatais, más nao há descriçao de achados necroscópicos. Ao lado do infiltrado linfocitário atípico observou-se também reaçao granulomatosa tuberculóide generalizada englobando infiltrado de padrao virchoviano com baciloscopia rica. Os autores acreditam que este quadro representaria uma reaçao reversa induzida pela "Síndrome da Sulfona".

Androgenic status in patients with lepromatous leprosy.

OBJECTIVE: To assess the incidence of testicular atrophy by evaluation of hormonal status, testicular histology and sperm production in chronic lepromatous patients. PATIENTS AND METHODS: Forty-one male patients with a mean age of 39.5 years (range 16-57) were studied at the Leprosy Hospital, Istanbul, Turkey, and were compared with 15 age-matched controls with proven fertility. RESULTS: Reduced testicular size was observed in 51% and gynaecomastia in 27%. Of the 31 patients who were married, 15 were primarily or secondarily infertile. Twelve of 16 patients had oligospermia or azoospermia. The mean basal luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol levels were significantly elevated and the level of testosterone significantly reduced when compared with the control group. CONCLUSION: Whenever leprosy is diagnosed patients should be informed of the need for treatment of an acute attack and the need for routine assessment of FSH, LH, testosterone and oestradiol levels to detect hypogonadism and potential infertility.

Testicular alterations in hansen's disease

Estudaram-se 58 fragmentos testiculares e o espermograma de 10 indivíduos normais e 24 hansenianos. Verificaram-se as alteraçöes gerais e precoces na histologia, a freqüência de espermátides jovens no lumem tubular e a medida dos diâmetros de 1.450 túbulos seminíferos. De acordo com os resultados obtidos, näo foi possível estabelecer uma correlaçäo qualitativa entre as descriçöes histológicas e ou quantitativa entre a morfometria, e um grupo clínico específico de hansenianos. Assim, também, a simultaneidade e a variabilidade dos achados observados em um mesmo testículo, se opöe às fases evolutivas, descritas por H. Grabstald & L.L. Swan e à classificaçäo proposta por B. Kumar et al. Os autores sugerem que as alteraçöes testiculares sejam conseqüência de uma auto-agressäo à glândula

Assessment of testicular volume in bacilliferous leprosy: correlation with clinical parameters.

Testicular involvement in leprosy was studied in 30 multi-bacillary (BL/LL) patients. Ten (33.3%) gave past history of type II reactions, of whom nine (30%) gave history of testicular pain and/or swelling. Decreased libido was a common complaint (63.3%). Gynaecomastia was noted in 3 patients (10%) and altered hair pattern in 11 patients (36.7%). Testicular sensation was impaired in 10 (33.3%) patients. Testicular volume was assessed objectively using the Prader orchidometer and found to be reduced in nine (30%) patients. Reduction in testicular volume correlated with longer duration of disease and a past history of type II reaction.

Male gonads in leprosy--a clinico-pathological study.

Sixty male leprosy patients (mean age 27.2 +/- 5.04 years) selected at random, were studied for gonadal involvement with the mean duration of illness 4.17 +/- 3.27 years. Only lerpomatous and borderline leprosy cases developed testicular and epididymal changes. Testicular pain and/or swelling (lepromatous 62.5%, borderline 30%) was the main presenting feature. Altered sexual function was observed in 34(56.6%) cases, and 11 patients revealed altered sexual hair pattern. Gynecomastia was seen in 9 cases. Reduced testicular size along with its soft feeling was present in 25% of cases while no testicular sensation was felt in 8 (13.3%) cases, and impaired testicular sensation in 9 (15%) of them. Spermogram revealed azoospermia in 19 (35%) and oligospermia in 16 (26.6%) cases. Histo-pathology revealed evidences of leprous pathology irrespective of testicular size, semen picture and clinical manifestations. There was marked variation in histopathological findings in testes and hence it was difficult to categorise them into vascular, interstitial and obliterative phase.

Endocrine testicular functions in leprosy.

Pituitary testicular functions were evaluated in leprosy. Forty-three men with leprosy were studied by basal estimations of plasma LH, FSH, Prolactin, Testosterone, 17-beta estradiol, metoclopramide stimulated prolactin responses and hCG stimulated testosterone responses. Fifteen young healthy men with proven fertility were studied as control subjects. The hormone estimations were related to the histologic changes observed in the testicular biopsies of leprous hypogonadism. In lepromatous leprosy (n:18) the basal plasma gonadotropin levels were significantly increased (FSH 29.5 +/- 2.3 mlU/ml; LH 21.5 +/- 1.9 mlU/ml, mean +/- SE). The plasma gonadotropins were in the normal range in tuberculoid leprosy. In borderline leprosy, the basal mean plasma FSH was normal, whereas LH levels were significantly increased (22.5 +/- 1.2 mlU/ml). The basal plasma testosterone levels were significantly decreased in lepromatous leprosy (1.6 +/- 0.12 ng/ml), tuberculoid leprosy (4.2 +/- 1.7 ng/ml) and borderline leprosy (1.8 +/- 0.18 ng/ml). The basal plasma 17-beta estradiol levels were significantly elevated in all the three types of leprosy. The basal plasma prolactin levels in plasma were significantly increased in lepromatous and tuberculoid leprosy. During hCG stimulation tests, the peak plasma testosterone responses were significantly reduced in both lepromatous leprosy and tuberculoid leprosy subjects. The blunted testosterone responses during hCG stimulation tests in leprosy correlated with the high basal 17-beta estradiol levels (r = 0.58; P less than 0.05). These results strongly suggest that hypogonadism in leprosy results from primary testicular failure. The significant elevation of plasma 17-beta estradiol levels in lepromatous, tuberculoid and borderline leprosy could play a role in hypogonadism of leprosy.