- Professor of Urology Medical faculty Belgrade. Now is working in Uromedica Polyclinic, Belgrade, Serbia, Main interest is andrology and general urologyedit
OBJECTIVE: To study L-carnitine (LC) and acetyl-L-carnitine (ALC) which are involved in energy metabolism and promote sperm motility and maturation. Studies have reported either no effect or that therapy with com- bined high dose L-C and... more
OBJECTIVE: To study L-carnitine (LC) and acetyl-L-carnitine (ALC) which are involved in energy metabolism and promote sperm motility and maturation. Studies have reported either no effect or that therapy with com- bined high dose L-C and ALC significantly increase sperm parameters (for- ward motility and concentration).
DESIGN: The study was randomized, double blind, placebo controlled (DBPC) and examined the effect of test formulation, Proxeed Plus, contain- ing L-C 2g and ALC 1g, as well as antioxidants, vitamins and minerals, in men with oligo-asthenozoospermia. The protocol was 2 months wash-out and 6 months treatment (T-2, T0, T+3, T+6), with test formulation (125 pa- tients) or placebo (50 patients).
MATERIALS AND METHODS: Men visiting the Andrology center, (18- 50 years) and with difficulty in conceiving >12 months, were randomized. Analysis of ejaculate was done according to WHO 5th guideline, and progres- sive sperm motility (A+B grade of rapid and progressive) was done manually. Statistical evaluation used McNemar-Boweker test, Spearman’s rank-order correlation test and Wilcoxon signed-rank test.
RESULTS: In the treated group there was statistically significant dif- ference, p= 0.004 by McNemar-Boweker test, of progressive sperm motility in the three different time periods: T0= 28.00% (12.00±38.00), T3=30.00% (12.00±39.00) and T6=31.00% (20.00±41.00) FIG 1.. The seminal plasma carnitine at T0 was 724.60 micromol/L (626.50±800.50) and at T6=782.80 micromol/L (686.6±926.30)FIG 2, and alpha glucosidase at T0 was 25,50 U/L (20.00±42.90) and at T6=32.60 U/L (23.00±42.80) FIG 3 and both these differences were significant (p< 0.014, by Wilcoxon signed-rank test). Further the Spearman’s rank-order correlation test showed that the increase of seminal carnitine (R=0.274; p < 0.023) and alpha glucosidase (R=0.246; p < 0.046) levels influenced the progressive sperm motility. Thus the correlation of seminal plasma carnitine (AUC= 0.726) and alpha glucosidase (AUC= 0.752) and progressive sperm motility showed that in man an increase of seminal carnitine of 7.7% (FIG 4 and 5) and alpha glucosidase of 12%, after six months therapy, would impact progressive sperm motility >10% with moderate accuracy (AUC= 0.726). In the placebo group there was no significant improvement in the progressive sperm motility.
CONCLUSIONS: This randomized DBPC study showed significant improvement in percentage of progressive sperm motility after six months of therapy and also underlines the importance of duration of therapy (3 and 6 months). The study demonstrated that an increase of seminal carnitine and glucosidase positively impacted upon the patient progressive sperm motility.
DESIGN: The study was randomized, double blind, placebo controlled (DBPC) and examined the effect of test formulation, Proxeed Plus, contain- ing L-C 2g and ALC 1g, as well as antioxidants, vitamins and minerals, in men with oligo-asthenozoospermia. The protocol was 2 months wash-out and 6 months treatment (T-2, T0, T+3, T+6), with test formulation (125 pa- tients) or placebo (50 patients).
MATERIALS AND METHODS: Men visiting the Andrology center, (18- 50 years) and with difficulty in conceiving >12 months, were randomized. Analysis of ejaculate was done according to WHO 5th guideline, and progres- sive sperm motility (A+B grade of rapid and progressive) was done manually. Statistical evaluation used McNemar-Boweker test, Spearman’s rank-order correlation test and Wilcoxon signed-rank test.
RESULTS: In the treated group there was statistically significant dif- ference, p= 0.004 by McNemar-Boweker test, of progressive sperm motility in the three different time periods: T0= 28.00% (12.00±38.00), T3=30.00% (12.00±39.00) and T6=31.00% (20.00±41.00) FIG 1.. The seminal plasma carnitine at T0 was 724.60 micromol/L (626.50±800.50) and at T6=782.80 micromol/L (686.6±926.30)FIG 2, and alpha glucosidase at T0 was 25,50 U/L (20.00±42.90) and at T6=32.60 U/L (23.00±42.80) FIG 3 and both these differences were significant (p< 0.014, by Wilcoxon signed-rank test). Further the Spearman’s rank-order correlation test showed that the increase of seminal carnitine (R=0.274; p < 0.023) and alpha glucosidase (R=0.246; p < 0.046) levels influenced the progressive sperm motility. Thus the correlation of seminal plasma carnitine (AUC= 0.726) and alpha glucosidase (AUC= 0.752) and progressive sperm motility showed that in man an increase of seminal carnitine of 7.7% (FIG 4 and 5) and alpha glucosidase of 12%, after six months therapy, would impact progressive sperm motility >10% with moderate accuracy (AUC= 0.726). In the placebo group there was no significant improvement in the progressive sperm motility.
CONCLUSIONS: This randomized DBPC study showed significant improvement in percentage of progressive sperm motility after six months of therapy and also underlines the importance of duration of therapy (3 and 6 months). The study demonstrated that an increase of seminal carnitine and glucosidase positively impacted upon the patient progressive sperm motility.
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. In order to further investigate the mode of action of clomiphene citrate, 5 oophorectomized women in the age range 28 to 41 years were followed with weekly determinations of serum FSH and LH for 20 weeks after the operation. They... more
. In order to further investigate the mode of action of clomiphene citrate, 5 oophorectomized women in the age range 28 to 41 years were followed with weekly determinations of serum FSH and LH for 20 weeks after the operation. They received no treatment during the first 4 weeks but during the next 16 weeks they were given estradiol 2 mgx2 daily orally, and from the 12th to the 16th week in addition clomiphene citrate 50 mgx2 daily. The high level of FSH after the oophorectomy decreased gradually during the treatment with estradiol alone, but this effect was partly neutralized by clomiphene citrate, as we observed a significant increase in FSH within 1 week of initiating treatment with clomiphene citrate. On the other hand, we did not find any significant changes in FSH within 4 weeks after treatment with clomiphene citrate was discontinued. The high level of LH after oophorectomy did not show any significant changes during the whole treatment period. It is concluded that clomiphene citrate primarily stimulated FSH secretion, most probably by a competition with estradiol for the receptor sites in the hypothalamus or the pituitary. In addition, it is concluded that clomiphene citrate has a prolonged effect, probably because of a tight binding to the receptor sites.
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Congenital absence of both vas deferens accounts for approximately 10% of cases of obstructive azoospermia. The purpose of the present study was to develop a treatment protocol for a group of azoospermic patients using surgical... more
Congenital absence of both vas deferens accounts for approximately 10% of cases of obstructive azoospermia. The purpose of the present study was to develop a treatment protocol for a group of azoospermic patients using surgical implantation of alloplastic spermatocoele to enable repeated sperm cell aspiration. Nine patients with congenital absence of both vas deferens, two with obstructed and one with destroyed vas, underwent surgery for the implantation of an alloplastic spermatocoele. In 10 of the 12 patients, vital spermatozoa were recovered from the aspirate and used for intrauterine insemination of their female partners with induced ovulation, some of whom then conceived.
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Cytogenetic analysis was performed in 80 patients with bladder tumor. The mitotic activity in patients with tumor G1, G2 and G3 degree of differentiation was not significantly different among them. Most of the patients with noninvasive... more
Cytogenetic analysis was performed in 80 patients with bladder tumor. The mitotic activity in patients with tumor G1, G2 and G3 degree of differentiation was not significantly different among them. Most of the patients with noninvasive tumor (G1) had a diploid or nearly diploid chromosome number, but all patients with invasive (G2 and G3) tumor had polyploidy. Marker chromosomes were found in 14 patients and 9 of them developed recurrence very soon. There is a good correlation between the recurrence rate and numerical or structural chromosomal abnormalities. This study emphasizes the importance of the chromosome analysis in the evaluation of therapy and prognosis for patients with bladder tumors.
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In a group of 270 infertile men serum FSH, LH and prolactin levels were estimated and testicular biopsy was done on all subjects. This investigation showed highly significant influence of histologic appearance on serum FSH and LH but not... more
In a group of 270 infertile men serum FSH, LH and prolactin levels were estimated and testicular biopsy was done on all subjects. This investigation showed highly significant influence of histologic appearance on serum FSH and LH but not on serum prolactin levels. Significant elevation of serum FSH level was first detected in men with spermatogenic arrest at the level of the primary spermatocyte, but the greatest number was in men without any germ cell in the seminiferous tubules. Serum LH level depended very much on the presence or absence of germ cells in the seminiferous tubules and were significantly elevated only in cases with seminiferous tubules deprived of the germ cells. According to this study serum FSH and LH levels were found to be good discriminator of testicular histologies.
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A comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height,... more
A comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base.
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Research Interests: Endocrinology, Infertility, Medicine, Humans, Prolactin, and 14 moreInternal Medicine, Testosterone, Hormones, Male, Androgens, Male Infertility, Azoospermia, Clinical Sciences, Androgen, Luteinizing Hormone, Estradiol, Follicle stimulating hormone, Oligospermia, and Paediatrics and reproductive medicine
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A total of 326 infertile men, 126 with genitourinary tract infection, and 200 without infection, were compared with 60 fertile men. Seminal plasma antisperm antibody with other clinical and microbiologic investigations were performed in... more
A total of 326 infertile men, 126 with genitourinary tract infection, and 200 without infection, were compared with 60 fertile men. Seminal plasma antisperm antibody with other clinical and microbiologic investigations were performed in all. Infertile men with genitourinary tract infection had antisperm antibody in 11.9 percent, infertile men without infection in 14.5 percent, and fertile men in 5 percent; these differences were not significant. The most common causes of these infections were gram-negative organisms and Chlamydia. Comparison of the levels of the titers of seminal plasma antisperm antibodies showed no significant difference between infertile and fertile men. This study shows no significant relationship between genitourinary tract infection and formation of the seminal antisperm antibody.
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Research Interests: Endocrinology, Biology, Medicine, Humans, Prolactin, and 15 moreInternal Medicine, Male, Klinefelter Syndrome, Karyotyping, tESTIS, Sertoli cells, Clinical Sciences, Middle Aged, Adult, Sperm Count, Sertoli Cell, Luteinizing Hormone, Follicle stimulating hormone, Endocrine System, and Paediatrics and reproductive medicine
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21 patients with chronic cystitis due to irradiation therapy for carcinoma of the cervix had symptomatic and cystoscopic improvement from instillations of early placental extract in saline. There was a statistically significant difference... more
21 patients with chronic cystitis due to irradiation therapy for carcinoma of the cervix had symptomatic and cystoscopic improvement from instillations of early placental extract in saline. There was a statistically significant difference between these patients and a control group.
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A 46,XX male (his condition ascertained through evaluation for infertility) underwent clinical, cytogenetic, and endocrinologic analyses, testicular biopsy, and had his permanent tooth sizes measured. The physical examination showed that... more
A 46,XX male (his condition ascertained through evaluation for infertility) underwent clinical, cytogenetic, and endocrinologic analyses, testicular biopsy, and had his permanent tooth sizes measured. The physical examination showed that the patient was smaller than normal and XXY males. The histologic picture was in accordance with well-known characteristics and meiotic analysis revealed no cells in division. The permanent tooth sizes were smaller than male controls. This finding suggests that the genes responsible for the testis-determining factor are present and that the genes influencing tooth size are absent in this patient.
Research Interests: Fertility, Medicine, Humans, Female, Male, and 6 moreKaryotyping, Male Infertility, tESTIS, Adult, Tooth, and Reference Values
A randomised group of 75 men with idiopathic oligoasthenozoospermia and asthenozoospermia were subjected to control study with kallikrein. Kallikrein was given to 45 men 600 units daily in a period of 3-6 months. The other group of 30... more
A randomised group of 75 men with idiopathic oligoasthenozoospermia and asthenozoospermia were subjected to control study with kallikrein. Kallikrein was given to 45 men 600 units daily in a period of 3-6 months. The other group of 30 infertile men was followed during the same period of time. Percentage of motile sperm was significantly improved after 3-6 months treatment with kallikrein. Sperm count and percentage of morphologically normal sperm showed improvement but was not statistically significant. Infertile men with sperm count below 20 X 10(6)/ml had greater improvement in sperm count than men with sperm count over 20 X 10(6)/ml. This study emphasizes that kallikrein is a relatively good drug for restoring sperm motility in idiopathic oligoasthenozoospermia and asthenozoospermia.
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Traditionally, the placenta with the fetal membranes and umbilical cord is treated as a mere by-product of the newborn baby. It seems little short of amazing that this harvest of human tissue delivered directly into the obstetricians’... more
Traditionally, the placenta with the fetal membranes and umbilical cord is treated as a mere by-product of the newborn baby. It seems little short of amazing that this harvest of human tissue delivered directly into the obstetricians’ hands is usually promptly discarded by them. It is the largest biopsy of healthy human tissue we can ever hope to obtain — so why does it fail to arouse interest, and for what reason does it remain relatively unexplored? In our view, examining its possible value in clinical medicine is important, and in this chapter we investigate some of its therapeutic potential.
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Serum levels of FSH, LH, prolactin, testosterone, and estradiol in 46 infertile men with hyperprolactinemia were compared with the same in 50 infertile and 30 fertile men with normal serum prolactin levels. Serum FSH levels in... more
Serum levels of FSH, LH, prolactin, testosterone, and estradiol in 46 infertile men with hyperprolactinemia were compared with the same in 50 infertile and 30 fertile men with normal serum prolactin levels. Serum FSH levels in hyperprolactinemic men were significantly higher than in the other groups, indicating disturbance of spermatogenic process among those men. Significantly raised serum LH levels were in infertile men with serum prolactin over 1000 U/liter. All men with hyperprolactinemia had significantly lower serum testosterone levels than other infertile and fertile men. Although serum testosterone was not under the lower limit of normal range and high LH levels demonstrated disturbance of Leydig cell function in hyperprolactinemic infertile men, serum estradiol levels were not different among investigated groups. Azoospermic men with raised serum prolactin had higher serum FSH and LH levels than oligospermic men with hyperprolactinemia. These data demonstrated disturbance in hypothalamopituitary-testicular axis in infertile men with hyperprolactinemia. Further studies of prolactin in males with reproductive failure could probably clear this problem.
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This study evaluates the clinical usefulness of one additional parameter for assessment of human sperm cell function in vitro--the hypoosmotic swelling test. The hypoosmotic swelling test evaluated the functional integrity of the sperm... more
This study evaluates the clinical usefulness of one additional parameter for assessment of human sperm cell function in vitro--the hypoosmotic swelling test. The hypoosmotic swelling test evaluated the functional integrity of the sperm plasma membrane. The investigation included a comparison of the hypoosmotic swelling test in samples containing motile and immotile spermatozoa and their correlation with the intrauterine insemination outcome. Motile spermatozoa expressed better membrane characteristics, without any importance of the hypoosmotic conditions. Positive correlation exists between HOS results and the outcome of IUI. This test can be a useful addition to the standard battery of semen analyzing tests.
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Spermatogenesis and meiotic chromosomal behaviour was analysed in a group of males aged 60-80 years. Decreased spermatogenesis was found in most of these aged men although individual differences existed. Chromosomal analysis of cells... more
Spermatogenesis and meiotic chromosomal behaviour was analysed in a group of males aged 60-80 years. Decreased spermatogenesis was found in most of these aged men although individual differences existed. Chromosomal analysis of cells undergoing diakinesis showed significantly lower chiasma frequency in elderly men, compared with a group of younger control males and also with infertile males.
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ABSTRACT
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An inherited (maternal origin) 13/14 translocation with the nucleolus organizer regions eliminated and one centromere was found in an oligospermic man whose wife had had two spontaneous abortions. Meiotic studies revealed all stages of... more
An inherited (maternal origin) 13/14 translocation with the nucleolus organizer regions eliminated and one centromere was found in an oligospermic man whose wife had had two spontaneous abortions. Meiotic studies revealed all stages of spermatogenesis with a trivalent configuration in diakinesis. Possible reasons for his subfertility and his mother&#39;s normal fertility are discussed.
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Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a... more
Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L-carnitine and L-acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double-blind, placebo-controlled clinical trial involved 175 males (19-44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p < 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p < 0.001) and the 3-month therapy (p = 0.014) in treated men. Increased seminal carnitine and α-glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation i...
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Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L‐carnitine and L‐acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a... more
Carnitine is essential for energy metabolism and spermatozoa maturation. Combining L‐carnitine and L‐acetylcarnitine with micronutrients has been investigated as a treatment for infertility in men. We evaluated the effects of a therapeutic formulation, Proxeed Plus, on sperm parameters in oligoasthenozoospermic men. This prospective, randomised, double‐blind, placebo‐controlled clinical trial involved 175 males (19–44 years) with idiopathic oligoasthenozoospermia who failed to impregnate their partners (12 months). Males received Proxeed Plus or placebo for 3 and 6 months. Sperm volume, progressive motility and vitality significantly (p < 0.001) improved after 6 months compared to baseline. Sperm DNA fragmentation index significantly decreased compared to baseline (p < 0.001) and the 3‐month therapy (p = 0.014) in treated men. Increased seminal carnitine and α‐glucosidase concentration also positively correlated with improved progressive motility. Decreased DNA fragmentation i...
The purpose of this study was to identify and quantify potential prognostic factors in treatment of suppurative renal infections which influence the outcome. For that purpose a retrospective review of 75 renal suppurative infection... more
The purpose of this study was to identify and quantify potential prognostic factors in treatment of suppurative renal infections which influence the outcome. For that purpose a retrospective review of 75 renal suppurative infection patients, at three tertiary Serbian clinics of urology from 1999 through January 2006, was conducted. This series comprised 49 women and 26 men, mean age 56.7 years, range 21–78. Patients were categorized into 3 groups according to the type of suppurative infections: a) unilocular renal or perirenal abscesses, b) pyonephrosis only and c) multiple renal or pyonephrosis infections along with extension on perirenal space. Additional classification was done according to favourable or unfavourable outcome (fatal outcome, unnecessary loss of kidneys or occurrence of recurrent infections which require nephrectomy). The following clinical characteristics were analyzed: demographic data, laboratory findings, comorbidity, infective complications, clinical course, t...
Prostate specific antigen (PSA) is one of the most significant specific tumor marker which is used for the detection and monitoring of prostate carcinoma. PSA exist in normal, adenomatous and cancerogenous prostate cells. The reference... more
Prostate specific antigen (PSA) is one of the most significant specific tumor marker which is used for the detection and monitoring of prostate carcinoma. PSA exist in normal, adenomatous and cancerogenous prostate cells. The reference range of PSA is 4 ng/mL. However, the presence of the elevated PSA level in blood does not confirm the presence of prostate cancer because the values PSA from 4.0 to 10.0 ng/mL appear in benign hyperplasio prostate (BPH) and carcinoma prostate. Evaluation of the free PSA and free to total PSA ratio (F/T) could improve discrimination between prostate cancer and benign prostatic disease. Of the total 60 patients enrolled in this study 18 had cancer and 42 had BPH. Serum total PSA and free PSA values were detected by Abbott tests. The prostates were examined by transrectal ultrasonografy (TRUS) and histologicaly confirmed by six-sectant biopsy. Serum detection of total PSA and free PSA was performed before treatment. In patients with total PSA values fro...
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The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×10⁶/mL of semen. Granular leukocytes when activated are capable of generating high... more
The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×10⁶/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with l...
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The diagnosis of an epididymal pathologic condition or an obstructive process at a different level is of relevant importance in treatment of infertile men. To date, carnitine and alpha glucosidase have been measured, but there is still... more
The diagnosis of an epididymal pathologic condition or an obstructive process at a different level is of relevant importance in treatment of infertile men. To date, carnitine and alpha glucosidase have been measured, but there is still debate over what information they can provide. This study compares seminal plasma carnitine and alpha glucosidase levels in 235 infertile men. The 235 subjects were divided into four groups according to their sperm concentration: azoospermic, severe oligospermic with sperm concentration below 1.0×10 6 /ml, oligospermic with sperm concentration over 1.1 to 20×10 6 /ml, and normospermic men with sperm concentration over 20×10 6 /ml and progressive motility over 30%. Each group of patients was divided into subgroups with low (below 500 nmol/ml) and high (over 500 nmol/ml) seminal carnitine level. This level of 500 nmol/ml in seminal plasma was determined by measuring of carnitine of 60 fertile men, which is 1 SD of seminal plasma carnitine level. A signi...
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Objective: White Blood Cells (WBC) are commonly present in almost every human semen sample, but the clinical significance of leukocytospermia, defined as more than 1 × 106/mL of WBC in seminal plasma, is not elucidated. The aim of this... more
Objective: White Blood Cells (WBC) are commonly present in almost every human semen sample, but the clinical significance of leukocytospermia, defined as more than 1 × 106/mL of WBC in seminal plasma, is not elucidated. The aim of this study was to evaluate the association of the leukocytospermia with sperm characteristics and biochemical markers of function of the male accessory glands in infertile men. Methods: One hundred and eighty-five men with fertility problems were investigated. They were composed of two groups, patients without leukocytospermia (n=115) and patients with leukocytospermia (n=70). The infertile men enrolled in the study underwent semen analysis and measurements of fructose, acid-phosphatase, zinc and γ- glutamyltranspeptidase in seminal plasma. Results: The mean age of study participants was 33.97 ± 6.45 years. The analysis of leukocyte concentration in semen has shown that 70 (37.8%) patients had leukocytospermia. Patients with leukocytospermia had significantly decreased sperm count and vitality while other sperm parameters such as seminal volume, progressive motility, morphology of pathological forms and seminal plasma pH were not affected. The levels of acid-phosphatase, fructose and γ-glutamyltranspeptidase were significantly decreased in infertile men with leukocytospermia compared to men without this condition. The levels of seminal zinc did not differ between the two groups of patients. Conclusion: Our results indicate that leukocytospermia has a significant negative effect on the standard semen parameters and biochemical compounds that reflect the function of accessory glands, prostate and seminal vesicles in particular.