Injection therapy for impotence

Injection of vasoactive drugs is an effective form of treatment for selected patients with impotence from virtually all causes. The two most commonly employed drugs in the United States are either papaverine alone or various combinations of papaverine and phentolamine. Patients with organic and mixed impotence are best suited for injection treatment, but selected patients with psychogenic impotence also benefit from therapy. After the patient is selected for injection therapy, he undergoes a series of trial injections in the physician's office. The incidence of priapism will be minimized if the initially administered doses are low and the patient is titrated to an appropriate dose level. Uncontrolled trials have revealed that injection treatment produces a satisfactory erection in 65 to 100 per cent of patients for a follow-up period of as long as 2 years with minimal side effects, but the dropout rate is high. If priapism does occur, it almost always responds readily to treatment with aspiration, low doses of an alpha-adrenergic agent, or both. The other common side effects are bruising or ecchymosis and nodule formation at the injection site. This latter complication has not been noted to cause significant abnormal penile curavature necessitating cessation of the program.     

Periosteal remodeling at the femoral neck in nonhuman primates.

Periosteal bone turnover is poorly understood. We documented intramembranous periosteal bone turnover in the femoral neck in intact nonhuman primates and an increase in osteoclast numbers at the periosteal surface in sex steroid-deficient animals. Our studies are the first to systematically document periosteal turnover at the femoral neck. INTRODUCTION: Bone size is an important determinant of bone strength, and cellular events at the periosteal surface could alter bone dimensions. We characterized periosteal cellular activity with dynamic histomorphometric studies of nonhuman primate femoral neck and shaft. MATERIALS AND METHODS: Femur specimens from 16 intact adult male and female nonhuman primates (Rhesus [Macaca mulatta, n = 9] and Japanese Macaque [Macaca fuscata, n = 7]) were analyzed. Animals were double-labeled with tetracycline, and necropsy was performed 2-7 days after the last dose. We characterized periosteal resorptive activity in an additional group of five intact and four castrate female animals. Multiple group comparisons in intact animals were performed by one-way ANOVA followed by a Fisher PLSD posthoc test. In gonadectomized animals, Fisher's exact test was used for dichotomous and Mann-Whitney U-test for continuous variables. RESULTS: Bone turnover in the periosteum of the femoral neck in intact animals was more rapid than at the femoral shaft but slower than in femoral neck cancellous bone. Similarly, in these intact animals, the eroded surface of cortical bone at the femoral neck periosteal surface was significantly greater than in the cancellous bone compartment (p < 0.0001) or on the femoral shaft (p < 0.0001). Gonadectomized female animals showed an increase in osteoclast number on the periosteal surface compared with intact controls (p < 0.01). CONCLUSIONS: We documented intramembranous periosteal bone turnover in the femoral neck by histomorphometric analyses. The tissue level bone formation rate was sufficient to add substantively to femoral neck size over time. Periosteal osteoclastic activity was not the result of the emergence of intracortical tunneling at the bone surface. Sex steroid deficiency produced an increase in osteoclast numbers at the periosteal surface. This is the first systematic documentation of periosteal turnover at the femoral neck.     

Antioxidant Activity of Limonene on Normal Murine Lymphocytes: Relation to H2O2 Modulation and Cell Proliferation

Abstract: Limonene is a monoterpene present in citrus fruit and is used as flavouring agents of foods. It was shown that monoterpenes possess antioxidant activity. Previously, it was demonstrated that limonene exerts anti‐proliferative action on a lymphoma cell line without modifying normal lymphocyte viability. H₂O₂ has a modulator role in cell proliferation. In the present study, the effect of limonene on normal lymphocytes proliferation and its relation with H₂O₂ level modulation was analysed, evaluating its effect on the activity of cell antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Limonene exerted a biphasic effect on cell proliferation; the increase in cell proliferation was related to the decrease in H₂O₂ level by the increase in catalase and peroxidase activities. Moreover, limonene protected the cells to the oxidative stress induced by exogenous addition of H₂O₂. In view of these results, it is possible that limonene could protect normal lymphocytes from diseases related to oxidative stress, including cancer, but further research is necessary to establish the role of limonene as a potential antioxidant that can effectively protect lymphocytes from oxidative stress and mitochondrial dysfunction.     

Flow Cytometric Analysis of Cellular Changes in Mice after Intradermal Inoculation with a Liposome–Iscom Adjuvanted Vaccine

As it is not known what changes to leucocyte homeostasis are mandatory for effective adjuvant action, the biological relevance of systemic changes elicited by different vaccine formulations can only be interpreted in the context of the immunological outcomes. We used flow cytometry to quantify the changes in leucocyte subsets induced in mice intradermally immunized with SAMA4 (adjuvant group), outer membrane proteins (OMP) purified from Actinobacillus pleuropneumoniae (OMP antigen group), SAMA4 adjuvanted OMP (OMP vaccine group), or phosphate-buffered saline (PBS: control group). This approach allowed direct comparisons to be made between the effects of antigen, adjuvant or antigen–adjuvant complexes on immune effector cell populations. Antigens complexed with the liposome–iscom hybrid adjuvant, SAMA4, generated strong antibody responses and cytotoxic T-cell activity in animals immunized intradermally, reflecting remobilization and recruitment of specific cell populations. Splenomegaly, due to granulocytosis, monocytosis and megakaryocytosis, was most prominent in the OMP vaccine group. Histological examination of spleen sections confirmed that these changes were due primarily to splenic haematopoiesis. Circulating numbers of granulocytes and monocytes increased significantly (P < 0.05) in the blood of the OMP vaccine group, as did granulocyte numbers in the lungs (P < 0.05). No changes in T- and B-cell numbers were detected by flow cytometry in the spleens, lungs or blood over the 28-day period in any treatment group. Thymocyte numbers (predominantly CD4⁺CD8⁺ cells) in the OMP vaccine group fell by 95% within 3 days of immunization. Identical cellular responses were obtained when an innocuous antigen, ovalbumin, was complexed with SAMA4 instead of OMP, thus demonstrating that the adjuvant effects of SAMA4 were due to synergistic interaction between antigen and adjuvant and not due to the presence of toxic components. The association of strong adaptive immune responses with such complex changes in leucocyte homeostasis induced by complexing adjuvant and antigen suggested that the changes were important for effective vaccination and were not purely circumstantial.     

Cloning and characterisation of the adenosyl phosphosulphate kinase gene from Aspergillus nidulans

The sD gene of Aspergillus nidulans has been cloned by heterologous screening of rationally selected cosmids. Co-transformation of the sD50 mutant JMP1 confirmed the presence of a functional gene. Sequence analysis determined this gene to be 680 bp in length, containing a 59-bp intron and encoding a protein of 206 amino acids. A protein-sequence comparison revealed a similarity to the C-terminal region of ATP sulphurylase, the sC gene product. Further sequence comparison revealed differences in a consensus sequence ATP-binding motif, indicating non-functionality of the APS kinase-like domain of ATP sulphurylase, and confirms sD as the gene encoding APS kinase in A. nidulans. Received: 17 April / 29 August 1997     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.