Lipid effects of an intrauterine levonorgestrel device or oral vs. vaginal natural progesterone in post-menopausal women treated with percutaneous estradiol

The clinical characteristics of 191 adolescent inpatients were examined in relation to frequency of previous suicide attempts, predictors of suicide attempts prior to hospitalization, and lifetime suicide attempts. Overall, more than 50% of the adolescent inpatients had attempted suicide during their lifetime, and of these more than half (58%) had made more than one attempt. Approximately half of the suicide attempters had made a serious attempt prior to hospitalization. Girls reported higher levels of depressive symptoms and suicidal ideation than boys, in addition to having attempted suicide prior to hospitalization (33%) or during lifetime (37%) more often than the boys (13% and 26%, respectively). Although about two thirds of the adolescent inpatients reported that they had received some help after a suicide attempt, approximately half of the repeaters had not received any help. The results of multivariate analyses showed that suicide attempts made prior to hospitalization were predicted by depressive symptom levels and a clinical diagnosis of depressive disorder, whereas frequency of lifetime suicide attempts was predicted by suicidal ideation levels and having a family member or a friend who had attempted (or committed) suicide. The high prevalence of lifetime and repeated suicide attempts among the psychiatric inpatients underscores the importance of identifying risk factors in the clinical evaluation of adolescent suicide attempters.     

Changes of the endometrium during oral hormonal contraception with ethinyl estradiol sulfonate and norethisterone acetate or d-noregestrel

48 fertile women took in three weeks 1 mg ethinylestradiolsulfonate weekly and in the 4th week 10 mg norethisterone acetate, respectively d-norgestrel in different dosages (0,5 mgs, 1,0 mgs, 1,5 mgs or 3,0 mgs). On this 48 women 69 abrasiones were made between the first and 37th treatment cycles in order to estimate the endometrium. Ethinylestradiolsulfonate caused for the most part a proliferation of endometrium, which reached to a glandulare cystic hyperplastic endometrium. We did not observe a reduction of the endometrial respond to this depot-estrogen in dependence on the time of taking. Norethisterone acetate and d-norgestrel effected on a different proliferated endometrium a secretory transfer mation always.     

Glucose and lipid metabolism during long-term antihypertensive treatment with indapamide in non-insulin-dependent diabetic patients

Thirty-nine patients with diabetes and hypertension were treated with indapamide for 24 weeks to study the effects of that drug on glucose and lipid metabolism. The drug was administered at a dose of 2 mg once per day in the morning as a single drug (26 patients) or in combination with other antihypertensive drugs (13 patients), including calcium antagonists, angiotensin-converting enzyme inhibitors, an alpha-blocker, or a beta-blocker. Blood pressure was reduced in both groups during treatment, and no alteration of glycemic control or lipid metabolism was observed. One patient complained of a mild headache, but treatment was continued. The results indicate that indapamide is useful for the long-term treatment of hypertension in diabetic patients, either alone or in combination with other antihypertensive agents.     

Systemic and histopathologic changes in Beagle dogs after chronic daily oral administration of synthetic (ethinyl estradiol) or natural (estradiol) estrogens, with special reference to the kidney and thyroid

ABSTRACT Four groups of 3 male and 3 female sexually mature Beagle dogs were treated daily po with either ethinyl estradiol (EE) or estradiol (E2). A fifth group of 4 males and 4 females acted as a control group. Three groups of dogs were treated with EE: One group was treated at dose levels of 2.0, 1.5, and 1.0 mg/kg for 6 mo; the other 2 groups received either 0.5 mg/kg or 1.0 mg/kg for 1 yr. The fourth group was treated with 5.0 mg/kg E2 for 1 yr. Results obtained for the clinical, hematological, and biochemical parameters and the histopathologic findings of most organs and tissues in EE- and E2-treated dogs were essentially comparable to those documented in the literature for dogs treated with synthetic or natural estrogens. Chronic treatment with EE or E2 induced similar effects, with the exception of mesothelial proliferation of the genital serosa, which was observed in EE-treated dogs only. Additional new estrogen-related findings were observed in the kidneys and thyroid glands of EE- and E2-treated dogs. Increased interstitial fibrous tissue occurred at the corticomedullary junction and in the outer cortex of the kidney. It appeared to originate primarily from the perivascular fibrous tissue of branches of the renal arteries and veins. Extension of this lesion into the renal parenchyma resulted in secondary atrophic changes of tubules and glomeruli. The treatment relationship and specific characteristics of this renal alteration differentiated it from other chronic renal interstitial and vascular diseases. Squamous metaplasia of urogenital tract epithelia, including renal cortical tubule epithelium, occurred as expected in both EE- and E2-treated dogs. Unexpectedly, squamous metaplasia of thyroid follicular epithelium also occurred. It was present in scattered follicles of both EE- and E2-treated dogs. The renal and thyroid changes did not alter clinicopathological function tests for either of these organs. These 2 new findings extend the list of estrogen-related effects in the dog.     

Arachidonate-induced thrombosis in mice: effects of gender or testosterone and estradiol administration

Sodium arachidonate (i.v.) has previously been shown to induce pulmonary emboli formation and a dose dependent cyanosis and respiratory depression in mice. Subsequently, we found that male mice are significantly more sensitive to arachidonate than females. Aspirin given orally 2 hours prior to arachidonate administration inhibits the responses of both males and females. Pretreatment with depo-testosterone markedly increases the effect of arachidonate in both males and females and depo-estradiol pretreatment reduces the responses in all mice. This exacerbation by testosterone of the arachidonate response and the attenuating effects of estradiol is consistent with data reported using other thrombogenic techniques.     

Successful treatment of pseudomyxoma peritonei using combination chemotherapy of intraperitoneal low-dose CDDP and oral 5'-DFUR administration

We report a case of pseudomyxoma peritonei treated with combination chemotherapy. A 73-year-old woman was diagnosed as having psuedomyxoma peritonei originated from the vermiform appendix. Appendectomy was performed, and 10 mg of MMC was administered intraperitoneally. From day 7, 600 mg/day of 5'-DFUR was orally given for 2 years, and 20 mg of CDDP once a month was intraperitoneally administered seven times. The patient has been doing well with no evidence of tumor recurrence for two years after operation. Combination chemotherapy with CDDP and 5'-DFUR, as a biochemical modulation therapy, has fewer side effects and leads to better quality of life of patients. We recommend a combination chemotherapy with low-dose CDDP and 5'-DFUR for patients in poor general condition.     

Effect of low estrogen combination oral contraceptive on metabolism of aspirin and phenylbutazone

Plasma levels of aspirin and phenylbutazone were estimated before and during administration of low estrogen combination type oral contraceptive for two menstrual cycles in ten and seven female volunteers, respectively. Aspirin was administered at doses of 300 and 600 mg, while phenylbutazone was administered at a dose of 400 mg. Blood samples were collected at intervals of 1, 2, 4, 6, and 8 h for aspirin and 2, 4, 6, 8, 24, 48, 72, and 80 h for phenylbutazone. Plasma levels, plasma half-life (t1/2), as well as area under curve (AUC) for aspirin after use of oral contraceptive revealed lower values. Phenylbutazone levels were not affected. Repeat studies of plasma t1/2 and AUC for aspirin after discontinuation of oral contraceptive showed values similar to basal levels.     

Behavior of the lipid and carbohydrate metabolism in patients with hypertriglyceridemia during exertion

In pateints with hypertriglyceridaemia in rest and during ergometer load an increased rate of lipolysis with increased metabolism of free fatty acids could be proved. This led to a disturbance of the glucose tolerance with hyperinsulinism and during muscle work to a limitation of the capacity of the oxidative glucose metabolism in musculature.     

Influence of ovariectomy and estradiol treatment on calcium homeostasis during aging in rats

Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.     

A clinical comparison of two triphasic oral contraceptives with levonorgestrel or norethindrone: a prospective, randomized, single-blind study

Menstrual bleeding patterns were investigated in young women taking either a levonorgestrel triphasic, Triquilar, or a norethindrone triphasic, Ortho 7/7/7, two commonly prescribed low-dose oral contraceptives. The levonorgestrel triphasic contains ethinyl estradiol (EE) 30 micrograms + levonorgestrel (LNG) 50 micrograms for the first six days, EE 40 micrograms + LNG 75 micrograms for the following five days, and EE 30 micrograms + LNG 125 micrograms for the last ten days. The norethindrone triphasic contains EE 35 micrograms + norethindrone (NET) 0.5 mg for the first seven days, EE 35 micrograms + NET 0.75 mg for the following seven days and EE 35 micrograms + NET 1.0 mg for the last seven days. Three hundred women from 16 to 25 years of age were randomized to the levonorgestrel triphasic (n = 150) or the norethindrone triphasic (n = 150) groups. Assessments were made from daily diary cards and from bimonthly investigator interviews over 6 pill cycles. The results showed a higher incidence of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone triphasic group (NET group) than in the levonorgestrel triphasic group (LNG group): 44.9% of patients (66/147) randomized to the LNG group reported intermenstrual bleeding one or more times during the study compared with 61.9% (91/147) randomized to the NET group (p = 0.0036). Furthermore, in subjects who did not miss any pills, the proportion of patients with intermenstrual bleeding in each cycle was significantly greater (p < 0.02, cycles 1-4, 6; p > 0.05, cycle 5) and was experienced for more days per cycle (p < 0.05, cycle 1) and for more cycles per patient (p < 0.05, 5 cycles) in the NET group compared with the LNG group. Intermenstrual bleeding was also less frequently observed in the LNG group than in the NET group in patients who missed pills (p < 0.05, cycles 3, 5 and 6). In addition, early withdrawal bleeding occurred more often in the NET group than in the LNG group (p < 0.05, cycles 1, 3 and 4). The incidence of amenorrhea was similar in both groups. These results demonstrate a significantly lower incidence of intermenstrual bleeding and therefore better cycle control with the levonorgestrel triphasic Triquilar, compared with the norethindrone triphasic Ortho 7/7/7.     

Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis

The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of murine toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates. In contrast, significant survival rates resulted when the same dose of IL-12 was used in combination the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls. Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.     

Suppression of adjuvant arthritis in rats by oral administration of type II collagen in combination with type I interferon

Foliar application of cytozyme to 30-day-old black-gram plants resulted 48% increase of dry matter accumulation. The increase in fresh and dry weights of total plants was largely due to enhanced CO2 assimilation rates which were associated with increased RuBP carboxylase activities. The photochemical characteristics in the isolated chloroplasts exhibited an increase of 32, 28 and 40%, measured as the photoreduction of DCPIP, FeCN and NADP, respectively. Cytozyme treatment also resulted an increase in the chlorophyll content in leaves.     

The effect of hyperthermia alone or in combination with actinomycin D on the RNA metabolism of solid tumors in children

The incorporation of 3H-uridine into the RNA was studied under normothermia 37 degrees C/120 min, hyperthermia 42.5 degrees/120 min, and both in combination with Actinomycin D by an autoradiographic in vitro method in 19 solid tumors of children: 6 Wilms' tumors, 5 neuroblastomas, 4 osteogenic sarcomas, and 4 different tumors. Hyperthermia invariably reduces the 3H-uridine incorporation into RNA by 11.7--86.4%, with an average of 47.5%. Actinomycin D consistently inhibits the 3H-uridine incorporation between 27.7 and 99.8%, with the average inhibition of 62.0% being far greater than that recorded for hyperthermia. The highest degree of 3H-uridine incorporation inhibition is obtained using hyperthermia in combination with Actinomycin D. The inhibition varies from 45.5--99.8%, with an average of 81.4%. In spite of the general regularity, the effect of hyperthermia and Actinomycin D are characterized by individual patterns. Obviously, they are dependent on proliferative activity rather than upon the particular type of tumor. The use of supranormal temperatures for the treatment of malignant tumors in man, also in combination with radiation or cytostatic drugs, is a possible and promising method of therapy.     

Bioavailability and pharmacokinetics of cyproterone acetate after oral administration of 2.0 mg cyproterone acetate in combination with 50 micrograms ethinyloestradiol to 6 young women

The bioavailability and pharmokinetics of cyproterone acetate (CA) were studied in 6 healthy young women. The subjects received a single oral dose of 2 mg carbon-14-CA plus 50 mcg tritiated-ethinyl estradiol. Matimum plasma levels of CA were observed about 4 hours after administration. During the 4-10 hours following administration, carbon-14-CA in plasma disappeared with a half-life of 3 + or -1.6 hours. The half-life for the subsequent phase of disposition was 1.7 + or -.5 days. The apparent volume of distribution for CA was 1300 + or -580 liters. Although plasma equivalents of carbon-14-CA had higher absolute values, the course of their distribution was similar to those concentrations for the unchanged drug. 88 + or -11% of the dose was recovered and 30.4 + or -7.3 excreted in urine. The concentration of the primary metabolite of CA in plasma showed a decline which paralleled the terminal disposition phase of CA; the elmination half-life being 1.8 + or -.1 days. The apparent distribution volume for the primary metabolite was 95 + or -25 liters. CA, in comparison with its primary metabolite, had 10 times the apparent distribution volume. Approximately 90% of CA was present at all times following administration. In terms of total activity, the proportion of CA in plasma remained constant 1/2 day after administration. It is suggested that the transfer of CA from tissues determines the rate of metabolization of CA and the excretion of metabolites.     

Homing potentials of circulating antibody-secreting cells after administration of oral or parenteral protein or polysaccharide vaccine in humans

The site of antigen encounter influences the Ig-distribution and homing potentials of circulating antibody-secreting cells (ASC) induced. After oral antigen administration, the majority ASC secrete the mucosal Ig-isotype, IgA, and all of them express the gut homing receptor (HR), alpha 4 beta 7, thus implying mucosal homing of these cells. Parenteral protein vaccine induces an IgG-dominated response with a low proportion of alpha 4 beta 7 expressing cells. However, a polysaccharide vaccine, even if administered parenterally, elicits an IgA-dominated response, hence suggesting homing to the mucosa. In order to study the influence of the nature of the antigen on the targeting of the ASC response, the present work compares the homing potentials of circulating ASC in humans after administration of an oral Salmonella Typhi Ty21a vaccine (antigen studied: O-9,12 polysaccharide), an oral recombinant cholera vaccine (antigen studied: cholera toxin B-subunit, CTB protein), a parenteral pneumococcal vaccine (antigen studied: Pnc capsular polysaccharide 19F) or a parenteral tetanus toxoid vaccine (antigen studied: TT protein). alpha 4 beta 7 was expressed on a higher proportion of ASC induced by oral O-9,12 (99%) and CTB (99%) than by parenteral Pnc (70%) or TT (63%). L-selectin, the peripheral lymph node HR, was expressed on a smaller proportion of ASC induced by O-9,12 (37%) or CTB (43%) than of those induced by Pnc (78%) or TT (81%). The results imply that even if the nature of the antigen has a profound effect on the Ig-distribution of the ASC response, it does not seem to influence the targeting of the response.     

Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty children with GHD, mean age 7.9 yr, participated in the study of bone metabolism and body composition; and an additional group of 17 GHD children, in the study of lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean tissue mass, bone mineral content, fat mass, and percentage body fat were expressed as SD scores (SDS), in comparison with normative data of the same population. Lumbar spine BMD and BMAD and total body BMD were all decreased at baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD SDS, already after 6 months of treatment. Lean tissue mass SDS increased continuously. Bone mineral content SDS started to increase after 6 months GHRx. Fat mass SDS decreased during the first 6 months of GHRx and remained stable thereafter. Biochemical parameters of bone formation and bone resorption did not differ from normal at baseline and increased during the first 6 months of GHRx. Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of treatment. In conclusion, children with GHD have decreased bone mass. BMD, together with height and lean tissue mass, increased during GHRx. GHRx had a beneficial effect on lipid metabolism.