Pamidronate alters the growth plate in the oim mouse model for osteogenesis imperfecta.

Bisphosphonates alleviate bone pain and fractures associated with osteogenesis imperfecta (OI). Using the oim mouse model to simulate variations in OI severity, the effect of pamidronate on bone growth was assessed. Homozygous (oim/oim) and heterozygous (oim/wt) mice from 4 to 12 weeks of age were given pamidronate at 0 mg/kg/wk (control), 1.25 mg/kg/wk (low) and 2.5 mg/kg/wk (high). Humerus and ulna lengths were reduced in oim/oim mice relative to those of the oim/wt. Further, the oim/oim genotype exhibited a 23.5% prevalence of fractures in these bones as compared to the 2.8% prevalence observed in the oim/wt mice. Pamidronate tended to reduce fracture prevalence in a dose dependent manner for the oim/oim genotype (p<0.08) but had no effect on the low fracture prevalence in oim/wtmice. The high dose of pamidronate reduced bone length in females of both genotypes but not males when compared to control (p<0.01). Pamidronate increased growth plate area (p<0.05) by increasing growth plate height, particularly the proliferative and hypertrophic zones, in both genotypes indicating reduced growth plate cell turnover. The increased area coincided with increased osteoclast numbers in the metaphyseal region (p<0.05) though when corrected for the greater mineralized surface area that accompanies bisphosphonate treatment, osteoclasts per surface area were reduced indicating reduced resorptive capacity. This study demonstrated that the effects of pamidronate were independent of the degree of collagen deficit and fracture prevalence was improved in the most severe OI model, the oim/oim genotype.

Bisphosphonate treatment in the oim mouse model alters bone modeling during growth.

Osteogenesis imperfecta (OI) is a heritable disease, which results from an abnormal amount or structure of Type I collagen. Bisphosphonates, a class of synthetic antiresorptive drugs, used in osteoporosis management, are also used to decrease fracture incidence and improve quality of life in children with OI. In this study, we used the oim mouse to test the hypotheses that pamidronate treatment during active growth (1) produces larger, stronger, stiffer long bone diaphyses without altering bone material properties, and (2) negatively impacts longitudinal bone growth. Our results indicate that femoral cross-sectional moment of inertia in the distal metaphysis tended to increase with pamidronate treatment and that the treated bones are thicker and structurally stiffer, but shorter than their control-dose counterparts.

Long Term Cyclic Pamidronate Reduces Bone Growth by Inhibiting Osteoclast Mediated Cartilage-to-Bone Turnover in the Mouse.

Bisphosphonates, used to treat diseases exhibiting increased osteoclast activity, reduce longitudinal bone growth through an as yet undefined mechanism. Pamidronate, an aminobisphosphonate, was given weekly to mice at 0, 1.25, or 2.50 mg/kg/wk beginning at 4 weeks of age. At 12 weeks of age, humeral length, growth plate area, regional chondrocyte cell numbers, chondrocyte apoptosis, TRAP stained osteoclast number, and osteoclast function assessed by cathepsin K immunohistochemistry were quantified. Humeral length was decreased in pamidronate treated mice compared to vehicle control mice, and correlated with greater growth plate areas reflecting greater proliferative and hypertrophic chondrocyte cell numbers with fewer hypertrophic cells undergoing apoptosis. Pamidronate treatment increased TRAP stained osteoclast numbers yet decreased cathepsin K indicating that pamidronate repressed osteoclast maturation and function. The data suggest that long term cyclic pamidronate treatment impairs bone growth by inhibition of osteoclast maturation thereby reducing cartilage-to-bone turnover within the growth plate.

Antioxidant properties of green and black tea, and their potential ability to retard the progression of eye lens cataract.

Aqueous extracts of green and black tea are shown to quench reactive oxygen species such as singlet oxygen, superoxide and hydroxyl radicals, prevent the oxidative cross-linking of test proteins and inhibit single strand breakage of DNA in whole cells. They are also seen to be able to counteract the oxidative insult mounted by cigarette smoke. In rats in which cataract was induced by subcutaneous injection of selenite, administration of green or black tea extracts led to a retardation of the progression of lens opacity, suggesting the potential cataracto-static ability of tea.

Synthesis and estimation of calorific value of a structured lipid-potential reduced calorie fat.

The majority of reduced calorie fats and fat substitutes available today, though similar in texture and flavor to natural fats, contain fatty acids that are not usually present in edible oils and fats and thus do not fully match the chemistry and functions of natural fats. For example, such products do not provide nutritionally important essential fatty acids (EFA). In this investigation, we prepared and evaluated a reduced calorie fat, prepared entirely from natural fats, taking advantage of the fact that long-chain saturated fatty acids (LCSFA), such as behenic acid (22:0), are poorly absorbed. Mustard oil (MO) and sunflower oil (SO) were used as substrates to yield a structured lipid (SL). The product, being derived from a natural vegetable oil, would thus provide EFA, as would a native fat, a feature not provided by the low-calorie fats available in the market. Erucic acid (22:1) was isolated from MO by a lipase (EC 3.1.1.3)-catalyzed reaction. It was then hydrogenated to behenic acid, the ethyl ester of which was subsequently enzymatically transesterified with SO to yield a plastic fat containing about 30-35% behenic acid. Absorption of this fat was studied in Wistar rats. In a preliminary single oral dose experiment, rats were fed equal amounts (2 mL) of SO and the SL. Plasma triacylglycerol (TAG) levels were estimated after 1, 2, and 3 h of feeding. The significantly lower concentration of plasma TAG in the 2-h sample, observed in the SL-fed group compared to the SO-fed group (P<0.001), indicated poor absorption of the SL. In order to estimate the calorific value of the SL, we conducted a restricted diet growth experiment over 21 d on weanling Wistar male rats with SO as caloric control. Diets for the test groups were modified by adding 5, 10, and 15% SO for the control groups, and 5 and 10% SL for the experimental groups. Food consumption of the test groups was restricted to 50% of the feed containing 5% SO that had been consumed by the ad libitum group the previous day. Body weights were recorded during the experiment. Calorific value of the SL was estimated by comparing the 21 st-d mean body weight gain of the control group with that of the experimental group. Estimated calorific value of the SL was 5.36 kcal/g. Most of the behenic acid fed was excreted, as indicated by the analysis of the fatty acids of plasma and fecal total lipid. A second growth experiment on ad libitum diet was conducted over 21 d on weanling Wistar male rats to compare the absorption behavior of the SL with that of natural oil. SO (10%) was added to the diet of the control group, and SL (10%) was added to the diet of the experimental group. Feed consumption, as well as body weights, was recorded during the experiment. The growth pattern of the experimental group was identical to that of the control group during the period of study. The mean feed intake (9.8 g/d/rat for the control group vs. 9.9 g/d/rat for the experimental group) indicated good palatability of the product. In conclusion, the enzymatically synthesized SL containing EFA and natural antioxidants has nutritional properties almost identical to those of natural fats, and can be used as a reduced calorie fat.

Cell death in exorbital lachrymal gland of anophthalmic mutant rat during postnatal development.

Regression in the exorbital lachrymal gland was observed in congenital blind mutant rats lacking eyeballs and optic nerves. The morphological changes during postnatal development in acinar cells of the lachrymal gland of mutant rats were compared with those of normal rats at day 13 (before the opening of the eyes), day 30 (15 days after opening of the eyes) and the adult (90 days). Atrophy of the lachrymal gland is most likely to be associated with absence of functional signals. During regression, there is a massive elimination of cells from the acini; no fibrosis or immune reaction (lymphocytic infiltration) was observed in the gland. This atrophy in the lachrymal gland of blind rats was not associated with the biochemical markers of apoptosis. Present observations indicate that cell elimination from the lachrymal gland in blind rats is a special type of apoptosis, where cell homeostasis is not required.

A behavioral profile of bilateral anophthalmic mutant rats.

A behavioral profile of hereditary bilateral anophthalmic mutant rat was studied in different light: dark schedules. The control and mutant rats were acclimatized to either a) a 12h light:12h dark cycle or b) continuous darkness or c) continuous illumination. The measurements of spontaneous motor activity with Opto Varimex and behavioral despair in a swim test were conducted. The daily food consumption and plasma glucose levels were also measured. The study indicated that, unlike the control rats, mutants did not exhibit any time dependent change in the spontaneous motor activity in any of the three different lighting conditions. A strong biphasic feeding burst was also not affected by anophthalmia in mutant rats. Our findings on spontaneous motor activity and the feeding pattern are contrary to those in the existing literature.

Oxidative damage to the eye lens caused by cigarette smoke and fuel smoke condensates.

Cigarette smoking is reported to increase the risk of cataract. Likewise, the use of smoky cooking fuel is implicated in the etiology of cataract. In an effort to understand the cellular and molecular basis, the in vitro and in vivo cataractogenetic effects of these smoke condensates have been studied using isolated rat lenses and pigmented rats. Isolated capsulated rat lenses are incubated with cigarette smoke condensate (CSC) and firewood smoke condensate (FSC) for varying periods, with and without antioxidants, in the presence and absence of light. CSC and FSC permeate the lens capsule, impart colour and opacify the lens in a light- and dose-dependent manner. Antioxidants offer partial inhibition against the above damage. The condensates contain polycyclic aromatics which generate reactive oxygen species such as O2 photodynamically, and ppb levels of Fenton metal ions which induce oxidative reactions through .OH. Smoke induced damage possibly occurs through systemic absorption and transport of toxic components to several tissues, and specially into the lens, wherein the turnover is slow, leading to chronic accumulation causing oxidative damage to the constituent molecules and to consequent lenticular opacity.

Possible antifertility agents belonging to substituted indoles.

Of the 21 compounds evaluated for antiimplantation and abortifacient activities, compounds (A1, A2, A4 and B1) and compounds (C1, C2, D1 and D3) were found to exhibit 40% and 30% antiimplantation activity, respectively, in female rats when given orally on days 1-5 postcoitum. The remaining 13 compounds were found to be inactive. All of the 21 compounds were also tested for the abortifacient activity, but all were found to be inactive.

Teratism induced in the developing chick by RPR-V, an organophosphate.

Fertile White Leghorn chicken eggs were injected on day 4 of incubation with 0, 0.25, 0.50 or 1.00 mg RPR-V/egg and opened on day 20 or allowed to hatch. The following parameters were examined: hatchability, growth and development, external malformations and skeletal deformities. As the dose was increased, the hatchability decreased, and the incidence of deformities increased. Staining of the skeleton with Alizarin red showed clear deformities in the embryos. The results suggest that RPR-V has teratogenic effects on chick embryos when injected on day 4 of incubation.

Pygomelia in a C3H/Crl mouse: case report.

Accessory hind limbs (pygomelia) were found in a male pup born in our colony of C3H/Crl mice. This malformation has not previously been reported in mice.

Antifertility efficacy of the plant Striga lutea (Scrophulariacae) on rats.

Acacetin and luteolin, the flavones isolated from the whole plant S. lutea, have been investigated for endocrine and contraceptive properties in the pre-implantation stage of pregnancy. Graded doses of these compounds, in gum acacia suspension, by oral administration from day 1 to day 4 of pregnancy showed dose-dependent anti-implantation activity (5-25 mg/kg body weight/day). MED100 was found to be 25 mg/kg body weight in the day 1-4 regimen in rats for both the compounds. In another study, a single oral dose of these compounds (10 mg/kg body weight) on day 1, 2 or 3 of pregnancy prevented 100% implantation. The compounds exhibited estrogenic property at their contraceptive dose level but failed to show antiestrogenic activity.

Antifertility activity of striga lutea--Part I.

The petroleum ether and chloroform extracts of the whole plant striga lutea have been found to possess significant antifertility activity in mice. Both these extract exhibited complete and partial resorption of implants at a dose of 100 mg/kg and 50 mg/kg body weight, respectively. Histological studies of the uterus and ovary were carried out to confirm the antifertility activity of these extracts.