Alginate oligosaccharides modify hyphal infiltration of Candida albicans in an in vitro model of invasive human candidosis.

AIMS: A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species. METHODS AND RESULTS: Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser scanning microscopy and histochemistry. Expression of candidal virulence factors was determined biochemically and by quantitative PCR (qPCR). Changes in surface charge of C. albicans following OligoG treatment were analysed using electrophoretic light scattering. OligoG induced marked alterations in hyphal formation in the substrate assays and reduced invasion in the epithelial model (P < 0·001). Significant dose-dependent inhibition of phospholipase activity in C. albicans was evident following OligoG treatment (P < 0·05). While OligoG binding failed to affect alterations in surface charge (P > 0·05), qPCR demonstrated a reduction in phospholipase B (PLB2) and SAPs (SAP4 and SAP6) expression. CONCLUSION: OligoG CF-5/20 reduced in vitro virulence factor expression and invasion by C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: These results, and the previously described potentiation of antifungal activity, define a potential therapeutic opportunity in the treatment of invasive candidal infections.

Locally aggressive granular cell tumor causing priapism of the crus of the clitoris. A light and ultrastructural study, with observations concerning the pathogenesis of fibrosis of the corpus cavernosum in priapism.

A case of focal priapism of the clitoris caused by a microscopic granular cell tumor (GCT) is described. This neoplasm is considered locally aggressive because it invades the lumens of peripheral cavernous sinuses of the crus of the clitoris. Caverns adjacent to those invaded by tumor exhibit stasis, telangiectasia, and necrosis of the smooth muscle of the trabecular wall. These alterations lead to telescoping collapse and compression of the cavernous spaces and culminate in fibrosis. Ultrastructurally, replicated basal lamina is found surrounding clusters of granular cells. We suspect that the multilayered lamina, in addition to being produced by tumor cells, is derived from the trabecular endothelium surrounding the caverns invaded by the GCT. The replication of the basal lamina may be provoked by cycles of injury and repair to these vessels caused by repeated episodes of prolonged vascular stasis. A peculiar large vein with perforating branches was observed in the center of the cavernous spaces of the crus. This vein is not found in normal crura and, therefore, represents a morphologic adaptation created to drain the cavernous spaces.

The obstetrical management of conjoined twins.

A pair of conjoined twins (thoracopagus) was delivered abdominally after antepartum diagnosis. Obstetrical planning is more likely to be successful with antepartum diagnosis, which can be done only if the possibility of conjoining is considered with each twin gestation. Once a twin gestation is suspected, ultrasonography should be performed for confirmation. Conjoined twins should be suspected in a gravid mother with multiple gestations and an abnormal fetal attitude. When the images cannot be separated on ultrasonography, amniographic examination, using a double contrast medium of oil-water, should demonstrate dye in the gastrointestinal tract and a union between the twins, as well as establish the presence of a monoamniotic sac. Because of increased fetal morbidity and mortality of vaginal delivery in monoamniotic twins, even if not conjoined, elective cesarean section at term will ensure the best chance for fetal survival.

Depo-medroxyprogesterone acetate as a contraceptive.

PIP: To test its effectiveness as a contraceptive, 150 mg of depo-medroxyprogesterone acetate (DMPA) was administered every 3 months to 752 women for 44 consecutive cycles. Side effects were similar to those seen with other contraceptive agents, the major one being irregular bleeding. During the course of this experiment, ethinyl was administered orally for 7 days of each month. This treatment improved the regularity of bleeding cycles. Although 450 women discontinued usage of DMPA for both drug-related and non-drug-related reasons, this study still showed DMPA to be an effective contraceptive. Only one method-failure occurred during 10,000 months of use; 75% of the women conceived within 12 months after discontinuing DMPA; 1 patient developed a questionable case of thrombophlebitis, but no cases of thromboembolic phenomenon were reported. DMPA, then, is regarded as an effective contraceptive that appears to inhibit the pituitary release of gonadotropins, and to alter the cervical mucus.^ieng

Effect of ascorbic acid supplementation on the sperm quality of smokers.

OBJECTIVE: To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality.

Simultaneously occurring condylomata acuminata, carcinoma in situ and verrucous carcinoma of the vulva and carcinoma in situ of the cervix in a young woman. A case report.

A case of simultaneously occurring condylomata acuminata, carcinoma in situ and verrucous carcinoma of the vulva and carcinoma in situ of the cervix was seen in a 26-year-old woman. In situ DNA hybridization on sections of the condyloma acuminata and verrucous carcinoma yielded DNA sequences for human papillomavirus 6.

Carcinoma in situ of the vulva. A clinicopathologic study of 50 cases.

The authors reviewed 50 cases of carcinoma in situ of the vulva treated at the University of Texas Medical Branch, Galveston, from 1975 to 1984. Sixty-two percent of the patients were premenopausal. The most frequent complaint was vulvar itching. Twenty-six percent of the patients were asymptomatic. Recurrences were frequent (25%) and were associated with multifocal lesions, involved surgical margins and the bowenoid histologic type. Superficially invasive carcinoma was detected in 8% of patients, mostly postmenopausal women with simplex histologic types. Immunohistochemical studies failed to detect papillomavirus- or herpesvirus-associated antigens in any of the cases. Follow-up of 48 patients from six months to ten years revealed no mortality from invasive cancer.

Seminal plasma trace metal levels in industrial workers.

This study compares the seminal plasma trace metal levels of hospital workers with groups of industrial workers in a petroleum refinery, smelter, and chemical plant. The metals measured were the essential metals (copper, zinc, nickel, cobalt, and manganese) and the toxic metals (lead, cadmium, and aluminum). The group mean +/- SE metal level for each group (50 subjects per group) was calculated, and the statistical significance of the group mean differences of the industrial groups with the hospital group (control) was determined by the Student's t-test. The differences observed in the smelter group were increased copper and zinc (p < or = 0.001) and decreased nickel, cobalt, and manganese (p < or = 0.001, < or = 0.01). The refinery group differences were increased copper, zinc, and nickel (p < or = 0.001) but decreased cobalt and manganese (p < or = 0.001). The chemical group differences were increased zinc (p < or = 0.001) and decreased cobalt (p < or = 0.001). The seminal plasma levels of the toxic metals lead and aluminum were increased in each of the industrial groups (p < or = 0.001). Concurrent differences were (1) decreased accumulation of nickel, cobalt, and manganese in the smelter group, (2) decreased cobalt and manganese in the refinery group, and (3) only decreased cobalt in the chemical group.

Comparison of sperm viability with seminal plasma metal levels.

This study compares the semen levels of lead (Pb), cadmium (Cd), and aluminum (Al) in relation to live sperm in semen samples from 64 apparently healthy men. The measured levels were separated into live sperm count tertiles (<25% [18 subjects], 25-50% [26 subjects], and >50% [20 subjects]). The mean +/- SD for each group was calculated, and the difference between the means of the high and low tertiles were compared by ANOVA. Significant differences were observed between the high and low live sperm groups for Pb (p < 0.01) and Al (p < 0.05), but not Cd. Spearman's rank correlation between sperm viability and the semen plasma metal levels showed a direct relation to Mg (p < 0.05). However, there was an inverse relation to lead (p < 0.001), cadmium (p < 0.01), and aluminum (p < 0.01). There was no significant correlation between Ca and Zn. Linear regression between the live sperm counts and semen level of the three metals show that metal levels were inversely correlated with the percentage of live sperm (p < 0.001, < 0.01). Apparently, the presence of these metals in the environment and in seminal plasma exerts a toxic effect on sperm.

An in vitro study of alginate oligomer therapies on oral biofilms.

OBJECTIVES: The in vitro effect of a novel, oligosaccharide nanomedicine OligoG against oral pathogen-related biofilms, both alone and in the presence of the conventional anti-bacterial agent triclosan, was evaluated. METHODS: The effect of OligoG±triclosan was assessed against established Streptococcus mutans and Porphyromonas gingivalis biofilms by bacterial counts and image analysis using LIVE/DEAD(®) staining and atomic force microscopy (AFM). The effect of triclosan and OligoG surface pre-treatments on bacterial attachment to titanium and polymethylmethacrylate was also studied. RESULTS: OligoG potentiated the antimicrobial effect of triclosan, particularly when used in combination at 0.3% against S. mutans grown in artificial saliva. OligoG was less effective against established P. gingivalis biofilms. However, attachment of P. gingivalis, to titanium in particular, was significantly reduced after surface pre-treatment with OligoG and triclosan at 0.01% when compared to controls. Light microscopy and AFM showed that OligoG was biocidal to P. gingivalis, but not S. mutans. CONCLUSIONS: OligoG and triclosan when used in combination produced an enhanced antimicrobial effect against two important oral pathogens and reduced bacterial attachment to dental materials such as titanium, even at reduced triclosan concentrations. Whilst the use of triclosan against oral bacteria has been widely documented, its synergistic use with OligoG described here, has not previously been reported. The use of lower concentrations of triclosan, if used in combination therapy with OligoG, could have environmental benefits. CLINICAL IMPORTANCE: The potentiation of antimicrobial agents by naturally occurring oligomers such as OligoG may represent a novel, safe adjunct to conventional oral hygiene and periodontal therapy. The ability of OligoG to inhibit the growth and impair bacterial adherence highlights its potential in the management of peri-implantitis.

Retropubic urethrocystopexy: vaginal approach.

A modification of the classic Marshall-Marchetti-Krantz (MMK) operation which includes suspending the urethrovesical junction to the pubis by the vaginal approach is presented. This offers the advantages of a shorter operating time, the lack of an abdominal incision, and the concomitant repair of other pelvic anatomic defects through the vagina, with a cure rate at least equal to, if not better than, that associated with the abdominal route. The study group of 25 patients had less morbidity, a 1-day decrease in hospital stay, and 1 1/2 fewer days of catheter drainage compared to a matched control group of MMK operations done abdominally in this preliminary report. A 96% cure and improvement rate of the symptoms of stress incontinence was shown at the 6-week postoperative visit. This compares to a 92% rate in the control series of abdominal MMKs. The permanency of the procedure will have to be evaluated critically as more cases are added and sufficient time elapses to see if these good initial results hold up.

Antioxidant capacity of lycopene-containing foods.

Increased consumption of tomatoes and tomato products has been associated with decreased cancer risks. One fat-soluble compound identified in tomatoes which may be responsible for this association is lycopene. There may, however, be other antioxidants present in tomato-based foods, and total antioxidant capacity may be another way to rate the health benefits of these foods. In this work, we examined the Trolox-equivalent antioxidant capacity (TEAC) of aqueous and organic extracts of lycopene-containing foods: ketchup, fresh tomatoes, tomato paste, tomato sauce, tomato soup, tomato juice, vegetable juice, canned tomatoes and watermelon. Antioxidant activity in these food extracts was greater in the aqueous versus organic fractions, except for watermelon and tomato sauce where the levels were similar in the two fractions. Lycopene levels in the food samples tested, however, were relatively greater in the organic fractions, with the exception of the two juices, which had similar levels in the two fractions, and two highly concentrated tomato products, tomato paste and ketchup, which had relatively higher lycopene levels in the aqueous fractions. The foods with the highest antioxidant capacity per serving overall (tomato soup was highest) did not have the highest lycopene levels. This indicates that it may be important to consume a variety of tomato-containing products in order to obtain the largest variety of dietary antioxidants possible.

The ultrastructural response of human endometrium to medroxyprogesterone acetate.

Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.

PIP: The ultrastructural response of human endometrium to medroxyprogesterone acetate was examined. 30 women were injected im with 150 mg of the compound in the middle of the menstrual cycle and assigned at random 2 different times to undergo endometrial biopsy. The endometrium samples, examined by light and electron microscopy, revealed an initial response of maturation and then inhibition. 50 days after injection the atrophic changes began to reverse and by Day 90 the tissue resembled normal proli ferative endometrium. The significance of a nuclear inclusion body which is present is unclear at this time. This dosage did not appear to exert marked influence on endometrium ultrastructure beyond 90 days.

Decreased response of human milk leukocytes to chemoattractant peptides.

To test the hypothesis that neutrophils and macrophages in human milk may not defend by classical inflammatory mechanisms, experiments were conducted to ascertain whether adherence, orientation, and directed motility of these leukocytes would be enhanced by exposure to chemoattractant peptides including N-formyl-L-methionyl-L-phenylalanine and N-formyl-L-methionyl-L-leucyl-L-phenylalanine and C5a generated from zymosan activated human serum. Adherence and spatial orientation were tested on coverglasses and in Zigmond chambers, and chemotaxis was examined by Boyden chambers and a subagarose technique. Whereas, the adherence, orientation, and directed movement of adult peripheral blood neutrophils and monocytes were significantly enhanced by those chemotactic agents, human milk leukocytes failed to respond. The failure of the response of human milk leukocytes was not due to alterations in maternal peripheral blood leukocytes but appeared to be due partially to inhibitors in human milk. The experiments suggest that human milk leukocytes may be modified in the mammary gland to protect by noninflammatory mechanisms.

A short-term, intensive workshop approach for the treatment of human sexual inadequacy.

A rapid treatment approach to common sexual dysfunctions has been used in treating 59 couples, including 74 symptomatic individuals. Using a multidisciplinary team approach in an intensive 2 1/2 day workshop format, symptom improvement has been obtained in 86.5% of the dysfunctional individuals, with complete symptom reversal in 63.5%. The intensive workshop format has resulted in a saving of both patient and professional time and is seen as a viable and successful alternative to more time-consuming approaches of treating various sexual dysfunctions.