Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study.

BACKGROUND: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. OBJECTIVES: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. METHODS: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). CONCLUSION: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.

Zinc acetate and lyophilized aloe barbadensis as vaginal contraceptive.

Twenty samples of fresh ejaculate, donated by healthy volunteers ranging in age from 20-30 years, were obtained from the Center for Fertility & Cryobiology, University of Missouri, Columbia, Missouri. Average semen volume was 2.49 ml; average sperm motility was 71.32%; and average sperm density was 113.71 x 10(6) /ml. Testing for spermicidal effectiveness of a 1% concentration of zinc acetate, zinc sulfate, zinc chloride, and zinc gluconate proved that only zinc acetate was spermicidal. It appears this is due to the acetate in zinc acetate which may decrease oxygen utilization by sperm. Zinc acetate in vitro was antiviral while lyophilized aloe barbadensis was not. Lyophilized aloe barbadensis at concentrations of 7.5% and 10% proved to be spermicidal due to the multiple micro elements (boron, barium, calcium, chromium, copper, iron, potassium, magnesium, manganese, phosphorus, and zinc) which were toxic to the tail causing instant immobilization. The two compounds did not irritate or cause ulceration of rabbit vaginal epithelium. These results suggest the possibility of using zinc acetate and lyophilized aloe barbadensis as a new, effective and safe vaginal contraceptive.

Zinc arginine, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight and DNA without affecting testicular function.

Zinc has been implicated in steroid endocrinology of the prostate gland; and 5 alpha-dihydrotestosterone (DHT) is believed to express androgenic responses in the prostate. To note the effect of neutralized zinc (zinc gluconate + arginine) on the prostate, 50 sexually mature rats, weighing 325 +/- 20 g, were divided into five groups as follows: (1) control, (2) sham, (3) castrated, and injected intraprostatically with (4) 10 mg neutralized zinc, and (5) 20 mg neutralized zinc. Results indicated significant reduction (P < 0.05) of prostate weight, 5 alpha-reductase activity, and total protein and DNA concentrations in treated prostate tissue; no significant change in weight and histological structure of testes, epididymides, and seminal vesicles; and no significant effect on progeny and blood testosterone level of treated animals. These results suggest that direct application of neutralized zinc to the prostate offers a new modality for treatment of prostatitis without affecting spermatogenesis.

Sterilization of dogs with intra-epididymal injection of zinc arginine.

Condoms and vasectomy are the only fertility control methods available to males. Fifty million surgical vasectomies have been performed worldwide. In spite of improvements in the surgical techniques, the widespread use of vasectomy is limited due mainly to fear of genital operation. Chemical sterilization offers a promising new approach as an alternative to surgery. Fifteen sexually mature, mixed breed, male dogs, 2-3 1/2 years of age and weighing 22 +/- 1.8 kg, were divided into two groups. Five control placebo animals were injected with 0.5 ml of saline into the cauda epididymis, and ten treated animals were injected with 0.5 ml of 50 mg of zinc arginine into the cauda epididymis. Semen analysis performed before injection showed no significant difference between control placebo and treated groups. The control placebo animals exhibited a significant reduction in sperm motility one month after injection, which returned to normal within two months, and no change in semen volume, sperm abnormalities, or sperm concentration analyzed monthly for twelve months. The zinc arginine-treated animals achieved azoospermia ninety days after injection. The dogs were sacrificed one year after injection. There was no significant reduction of reproductive organ weights of the treated group as compared to the control placebo group. Although histological examination of the testes revealed normal seminiferous tubules, there was atrophy of the rete testes of the zinc arginine-treated group and, thus, increase in connective tissue. Histological examination of epididymides of the zinc arginine-treated group indicated that none of the cells in the head, body, and tail of the epididymis and ductus deferens contained sperm; 90% of the coils were empty and 10% contained amorphous pink cell debris; the coils decreased in diameter and were lined by cuboidal to columnar epithelium; no granuloma was observed. There was no significant change in serum testosterone level of control placebo and treated groups. These results offer the possibility of a new method of permanent sterilization instead of surgery. Zinc is considered to be nonmutagenic, noncarcinogenic, and nonteratogenic.

Value of intraprostatic injection of zinc and vitamin C and of ultrasound application in infertile men with chronic prostatitis.

Seventy infertile men with chronic prostatitis were treated by prostatic massage and wide-spectrum chemotherapy as basic treatment to which intraprostatic injection of zinc or vitamin C with or without ultrasound application was added as a new line of treatment. Comparison showed no significant improvement of the additive treatment over the conventional treatment used alone. Pus cells in the expressed prostatic smear diminished significantly after treatment, which was associated with significant increase of percentage of motile spermatozoa and significant decrease of abnormal forms. Bacterial flora was studied in comparison with findings in 20 cases of infertile males without prostatitis; staphylococci predominated in both patient and control groups.

Pharmacokinetics of zinc tannate after intratesticular injection.

Forty-eight sexually mature male rats were injected intratesticularly with either 1, 3, or 6 mg zinc tannate (Kastrin) or with saline (as control). Zinc localized only in low concentration in primary spermatocytes and could not be detected in spermatogonia, Sertoli cells, spermatids, or spermatozoa. Forty-eight hours after injection of 1 mg Kastrin, zinc was accumulated in the spermatogonia and primary spermatocytes while, after injection of 3 mg, zinc was preferentially localized in Sertoli cells and spermatids; however, zinc was observed in the spermatids and spermatozoa 48 h after injection with 6 mg, and germ cells lost their identity and were fragmented after 1 week.

Treatment of asthenozoospermia by intratesticular testosterone therapy.

A single intratesticular injection of 0.5 cc of 50 mg/ml of an aqueous testosterone suspension was administered to 14 patients with asthenozoospermia. In 7 cases, injection was combined with ultrasound of 0.5 w/cm2 for 2 min weekly for 4 weeks. In another 4 cases, only ultrasound was applied. Intratesticular injection with or without ultrasound caused a significant increase of motility percentage. Sperm density improved in cases that were associated with oligozoospermia (less than 20 million/ml). Ultrasound therapy (0.5 w/cm2 for 2 min) used alone had no effect on semen parameters. Associated hormonal changes in blood plasma were evaluated.

Chemical sterilization in the male part I: rats.

Adult male rats were injected intratesticularly with 3 mg and 6 mg zinc tannate (Kastrin) into each testis. Light microscopy and electron microscopy revealed that Kastrin is an effective irreversible chemical sterilant. Histological sections of testis indicated complete destruction of seminiferous tubules. Progeny testing of treated rats during a one-year period produced no pregnancy. No epididymitis or testicular teratoma were observed. Blood testosterone level of rats treated with 3 mg zinc tannate did not change significantly; however, in rats treated with 6 mg zinc tannate, blood testosterone level decreased significantly by 79% (p less than 0.0001).

Effect of Panax ginseng on testosterone level and prostate in male rats.

Adult male rats were treated with 1% and 5% Panax Ginseng in their diet for 60 days. Control rats were used. There was an increase in daily food consumption without an increase in body weight of treated animals. Rats that received 5% ginseng experienced a significant increase in blood testosterone level (rho less than 0.001). Prostate weight in the treated animals was significantly reduced as compared to the control animals.

Effects of subtoxic levels of lead and cadmium on urogenital organs of male rats.

Higher incidence of prostate cancer among lead and cadmium smelter workers has been reported. Forty male rats were divided into four groups. Group I served as control; Group II was injected intraperitoneally, close to the site of the prostate, with 0.05 mg lead acetate; Group III was injected with 0.05 mg cadmium chloride; and Group IV was injected with a combination of 0.025 mg lead and 0.025 mg cadmium chloride. After daily injection for one month, lead and cadmium had a synergistic effect on testicular damage and prostatic cytology; although no tumor formation was observed in the prostate, there was replacement of columnar epithelium by squamous epithelium, suggestive of progressive, precancerous changes. There was an increase in incidence of stone formation in the kidney and urinary bladder.

Effect of acute and chronic simulated high altitude on male reproduction and testosterone level.

Forty, sexually mature, male rats were divided into two control and two treated groups. One of the treated groups was exposed five times to 6000 m of high altitude (acute exposure), and the other treated group was exposed 70 times (chronic exposure). Acute exposure had no pathological effect on the male reproductive tract or blood testosterone level; however, in animals that received chronic exposure, there was significant reduction in plasma testosterone level, 80% of spermatogenic tissue was highly vacuolated, nuclei of the interstitial tissue revealed pyknosis, and dilation of the blood vessels was noted throughout the testis.

Treatment of genital herpes simplex virus in male patients.

Twenty-three male patients with herpes simplex virus type 2 blisters on the prepuce, glans penis, and penile shaft were divided into 2 groups. Ten patients served as controls, and thirteen patients were treated with ultrasound (1 W/cm2 for 60 sec) and Herpigon on 3 consecutive days. Results showed a negative virus culture after 3 days of treatment and significant reduction of the recurrent infection in the treated group while the control group experienced recurrent infection within 62--80 days. This method offers a new therapeutic treatment for genital herpes simplex virus.

New treatment for herpes simplex virus type 2 [ultrasound and zinc, urea and tannic acid ointment]. Part II: Female patients.

Clinical treatment of 147 female patients suffering with genital herpes simplex virus were conducted in two phases. The purpose of Phase I was to note the efficacy of treatment with ultrasound and Herpigon ointment (zinc, urea, and tannic acid) in relieving pain and shortening the length of time involved in healing. Results indicated that the combined treatment significantly reduced pain and length of healing period. Phase II involved a 2-year follow-up of patients with primary and recurrent infection. Results indicated that the combined treatment significantly reduced recurrent infection in all patients treated.

Local male hormonal therapy in male infertility: a preliminary report.

The therapeutic effect of local infiltration of the testis by testosterone crystalline suspension was studied in 18 cases of severe oligozoospermia. Evaluation was done by semen analysis follow-up, and results were correlated with preoperative testicular biopsies. About 40% of the cases showed improvement of sperm count and/or motility. Testicular biopsies of responding cases showed mild inhibitory changes, such as sloughing or partial spermatogenic arrest at late stages, while cases with tubular hyalinization or spermatogenic arrest at the stage of spermatogonia showed no response. The method proved to be simple, safe, and promising.

Effect of ultrasound on testicular electrolytes (sodium and potassium).

The testes of 50 rats were placed in a cup filled with water and received 1 W/cm2 of ultrasound for 15 min. Fluid was collected from the seminiferous tubules and rete testis of the treated and control groups at 1, 8, 12, and 24 hr intervals. Ultrasound increased the sodium concentration in the fluid of the seminiferous tubules, decreased the sodium concentration in the fluid of the rete testis, increased the potassium concentration in the fluid of the rete testis, and decreased the potassium concentration in the fluid of the seminiferous tubules. Fourteen, slightly sedated, monkeys (Macaca fascicularis) were treated with 1/2 W/cm2 of ultrasound for 30 min. Water was used as the coupling agent for seven monkeys and 3% NaCl was used as the coupling agent for the other seven monkeys. The efficacy of ultrasound treatment in reducing sperm count to zero and achieving zero motility was increased when 3% NaCl was used. Sperm count was at the level of presonication after 20 weeks when water was used as a coupling agent.

Ultrasound as a new method of male contraception.

Twenty male cats were treated once or twice with 1 watt/sq cm of ultrasound for 10 minutes. Each of 24 male dogs received one to three treatments with 1 watt/sq cm for 10 minutes. Another six dogs were treated with 2 watts/sq cm for 15 minutes. Four Cebus apella monkeys were treated with the same dosage as that used for the cats and dogs. A dosage of 1 watt/sq cm for 10 minutes was also applied to four human patients without the use of anesthetics, and no pain or side effects were noted. In all treated animals as well as in human patients the results indicate that ultrasound significantly suppresses spermatogenesis according to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.

PIP: Ultrasound was tested as a method of sterilization in cats, dogs, monkeys, and humans, utilizing an ultrasound machine manufactured by Whitewater Electronics specifically for this research. 30 male cats were divided into 3 groups, 2 experimental and 1 control. The treated groups received 1 watt/sq cm for 10 minutes once, or a 2nd time after 48 hours. Testicular biopsies were made 60 days after treatment. 24 male dogs were divided into 3 groups receiving either 1,2, or 3 treatments within a 1-week interval with 1 watt/sq cm for 10 minutes. Sperm counts were made for 5 consecutive weeks preceding ultrasound treatment and semen analyses made weekly. 6 dogs were treated with 2 watts/sq cm for 15 minutes. Antibodies to spermatozoa were determined by the Kibrick method. 4 South African monkeys were treated with 1 watt/sq cm for 10 minutes; testicular biopsies were obtained 1 month before treatment and 60 days after treatment. 1 watt/sq cm for 10 minutes. Testicular biopsies were obtained 3 weeks before treatment and orchiectomies were performed 14 -17 days after treatment. In all treated animals and human patients, ultrasound significantly suppresses spermatogenesis accoridng to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.

Effects of sonication on mature rat testes.

Exposure of rat testes to high-frequency sound waves temporarily interrupted the spermatogenic process. Rats treated with 1 watt/sq cm for 10 minutes exhibited a degeneration of advanced germinal cells and were incapable of impregnating females for 150 days. Forty-eight hours after sonication, spermatocytes and spermatids developed irregular membranes and released their contents into theinterstitium. Spermatogonia, Sertoli cells, and Leydig cells appeared normal, and no genetic anomalies could be detected in the progeny of treated animals. It was hypothesized that the reduction in sperm count was due to changes in membrane permeability which produced conditions unfavorable to maturation of testicular cells.

Effects of subtoxic lead levels on pregnant women in the state of Missouri.

Cords, placentas, placental membranes, and maternal and fetal blood were collected from 249 women delivered in Columbia, Missouri (Region I). The same samples were obtained from 253 women delivered in Rolla, Missouri (Region II), near lead mining areas. The incidence of term pregnancies with early membrane rupture was 0.41% in Region I and 17% in Region II. The incidence of premature deliveries was 3% and 13.04% respectively. Lead concentration in blood and placental tissues of term pregnancies revealed no significant changes. In term with early membrane rupture, blood concentration of lead was higher, as was the case in placental tissues and cord. Lead concentration was highest in membrane tissues, in mug/100 grams (Regions I and II respectively): placenta, 6.0 +/- 0.01 and 7.0 +/- 0.03; cord, 11.0 +/- 0.34 and 12.0 +/- 0.18; membrane, 38.9 +/- 2.64 and 45.3 +/- 3.12. A high positive correlation (r = 0.2941) between lead concentration in maternal and fetal blood existed. Both were significantly (P less than 0.01) higher in preterm pregnancies and early membrane ruptures than in term pregnancies. These data suggest that subtoxic levels of lead could increase the incidence of early membrane rupture and premature deliveries.