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Biomedical subjects

C V Rao

Publications and source records attributed to C V Rao.

At least 73 records · Page 4Linked to original sources

Experimental evaluation of Bocopa monniera on rat gastric ulceration and secretion.

The anti-ulcerogenic effect of fresh juice from the whole plant of Bocapa monniera Wettst. (BMJ) commonly known as Brahmi in Hindi was examined using gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. Bocapa monniera juice (BMJ) at doses of 100 and 300 mg/kg and sucralfate at a dose of 250 mg/kg were given orally, twice daily for 5 days. BMJ 100-300 mg/kg produced significant antiulcer activity in all the experimental gastric ulcer models except in case of ethanol-induced ulcers where 100 mg/kg was not found to decrease it significantly. BMJ (100-300 mg/kg) was found to have little or no effect on the offensive acid-pepsin secretion, while cell shedding (microgram DNA/mg of protein) and mucin secretion in terms of total carbohydrates:protein ration (TC:P), the two important parameters of defensive factors were significantly decreased and increased respectively indicating enhancement of protective mucosal factors. Both BMJ (300 mg/kg) and SF showed tendency to increase the mucosal glycoproteins in terms of TC:P, though individual carbohydrates and total carbohydrates were either increased or showed a tendency to increase. Thus, ulcer protective effect of BMJ may be due to its effect on mucosal defensive factors like enhanced mucin secretion, mucosal glycoprotein and decreased cell shedding rather than on offensive factors such as acid and pepsin.

Animals↗

Effect of Piper longum Linn, Zingiber officianalis Linn and Ferula species on gastric ulceration and secretion in rats.

Use of Dipaniya Mahakasaya, a group consisting of 10 herbal drugs, has been suggested in Charaka Samhita to improve digestion. Out of these 10 plants, three, viz. P. longum (water decoction), Z. officianalis (water decoction) and Ferula species (colloidal solution) were studied for their antiulcer and mechanism of antiulcer effects in rats. All the drugs in the dose of 50 mg/kg, p.o., 60 min prior to experiment, showed significant protection against gastric ulcers induced by 2 hr cold restraint stress, aspirin (200 mg/kg, 4 hr) and 4 hr pylorus ligation. The antiulcerogenic effect seemed to be due to the augmentation of mucin secretion and decreased cell shedding rather than offensive acid and pepsin secretion which however, were found to be increased by them.

Animals↗

Chemopreventive efficacy of sulindac sulfone against colon cancer depends on time of administration during carcinogenic process.

Epidemiological and model studies with laboratory animals have provided evidence that nonsteroidal anti-inflammatory drugs reduce the risk of colon cancer. Sulindac, a nonsteroidal anti-inflammatory drug, has been shown to inhibit azoxymethane (AOM)-induced colon carcinogenesis in rats when administered continuously before, during, and after carcinogen treatment (initiation and postinitiation periods) or when given continuously beginning 14 weeks after carcinogen administration (promotion/ progression stage). The present study was designed to investigate the chemopreventive efficacy of sulindac sulfone (exisulind), the sulfone metabolite of sulindac, when administered during the promotion/progression stage of colon carcinogenesis in comparison to the effect during the initiation and postinitiation periods. We have also studied the modulating effect of exisulind on colonic tumor apoptosis. At 5 weeks of age, groups of male F344 rats were fed diets containing 0%, 0.06%, and 0.12% exisulind. At 7 weeks of age, groups of animals were injected s.c. with AOM (15 mg/kg body weight, once weekly for 2 weeks). Animals intended for the promotion/progression study and receiving 0% exisulind were switched to an experimental diet containing 0.12% exisulind at 14 weeks after the second AOM treatment. All rats remained on their respective dietary regimens until the termination of the study, 50 weeks after the second AOM injection. Colon tumors were evaluated histopathologically for tumor type. Administration of 0.06% and 0.12% exisulind during the initiation and postinitiation periods significantly inhibited the incidence and multiplicity of invasive and/or noninvasive adenocarcinomas of the colon. The inhibition of colon tumorigenesis by exisulind was associated with a significant retardation of body weight gain shortly after sulfone administration and increased apoptosis in the colon tumors. In contrast, administration of the higher dose (0.12%) of exisulind during the promotion/progression stage had only minimal effects on colon tumorigenesis and apoptosis in the colon tumors, suggesting that early administration, but not late administration, may be required for chemopreventive efficacy of this drug.

Adenocarcinoma↗

The inhibitory effect of hCG on counter current transfer of GnRH and the presence of LH/hCG receptors in the perihypophyseal cavernous sinus--carotid rete vascular complex of ewes.

The existence of the hormone passage from venous blood into arterial blood in the area of the perihypophyseal vascular complex has been demonstrated in some mammals, but its mechanism has not been defined. To study the regulatory mechanism we infused hCG into perihypophyseal cavernous sinus of ovariectomized, conscious ewes to test if the hCG would affect putative LH/hCG receptors and inhibit counter-current transfer of GnRH from the venous cavernous sinus to the arterial carotid rete. The latter study was done on an isolated head model. Ewes were ovariectomized in mid-anestrus and, after 4 to 5 wk were used in the experiments. On the day of experiment ewes were treated intramuscularly with estradiol benzoate or oil vehicle, and 18 to 20 h later were infused either with a multielectrolyte solution or hCG for 2 h via the venae angularis oculi. Immediately thereafter the ewes were anesthetized and exanguinated, and subsequently decapitated. The isolated head was perfused with Dextran in multielectrolyte. The 125I-GnRH was infused into the cavernous sinus via the venae angularis oculi for 5 min; contemporaneous samples were taken from the carotid rete and both jugular veins at 1-min intervals. Transfer of 125I-GnRH from the cavernous sinus to the carotid rete was inhibited by hCG in ewes pretreated with estradiol benzoate but not with oil (P<0.005). We collected tissue samples from the vascular complex of the cavernous sinus and carotid rete of cyclic ewes to determine the presence of LH/hCG receptors. In situ hybridization showed the presence of LH/hCG receptor mRNA transcripts in the walls of both arterial and venous compartments of the cavernous sinus-carotid rete complex, and immunohistochemistry revealed the presence of receptor proteins. These novel findings confirm previously obtained data suggesting that LH is a modulatory factor for the counter-current transfer of neuropeptides from the venous blood of the cavernous sinus to the arterial blood supplying the brain and hypophysis. The LH could modulate 125I-GnRH transfer acting directly on the vascular smooth muscle.

Animals↗

Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer.

Curcumin, derived from the rhizome of Curcuma longa L. and having both antioxidant and anti-inflammatory properties, inhibits chemically induced carcinogenesis in the skin, forestomach, and colon when it is administered during initiation and/or postinitiation stages. This study was designed to investigate the chemopreventive action of curcumin when it is administered (late in the premalignant stage) during the promotion/progression stage of colon carcinogenesis in male F344 rats. We also studied the modulating effect of this agent on apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats were fed a control diet containing no curcumin and an experimental AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%). At 7 and 8 weeks of age, rats intended for carcinogen treatment were given s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight per week. Animals destined for the promotion/progression study received the AIN-76A control diet for 14 weeks after the second AOM treatment and were then switched to diets containing 0.2 and 0.6% curcumin. Premalignant lesions in the colon would have developed by week 14 following AOM treatment. They continued to receive their respective diets until 52 weeks after carcinogen treatment and were then sacrificed. The results confirmed our earlier study in that administration of 0.2% curcumin during both the initiation and postinitiation periods significantly inhibited colon tumorigenesis. In addition, administration of 0.2% and of 0.6% of the synthetic curcumin in the diet during the promotion/progression stage significantly suppressed the incidence and multiplicity of noninvasive adenocarcinomas and also strongly inhibited the multiplicity of invasive adenocarcinomas of the colon. The inhibition of adenocarcinomas of the colon was, in fact, dose dependent. Administration of curcumin to the rats during the initiation and postinitiation stages and throughout the promotion/progression stage increased apoptosis in the colon tumors as compared to colon tumors in the groups receiving AOM and the control diet. Thus, chemopreventive activity of curcumin is observed when it is administered prior to, during, and after carcinogen treatment as well as when it is given only during the promotion/progression phase (starting late in premalignant stage) of colon carcinogenesis.

Animals↗

Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua.

Human endometrial stromal cells contain luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors and treatment with highly purified hCG results in an up-regulation of cyclooxygenase-2 (COX-2) gene expression and increased production of prostaglandin (PG) E2. Since PGE2 promotes the differentiation of endometrial stromal cells into decidua, we tested the hypothesis that LH and hCG themselves may promote this process. The results revealed that these hormones can promote morphological as well as functional differentiation. While their action on morphological differentiation did not require the presence of estradiol (E2) and progesterone (P4), they did require them for the functional differentiation. The hCG effect was mimicked by LH, but not by follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH) or alpha and beta subunits of hCG, suggesting that the hCG action was hormone specific and requires the conformation of native hormone. The hCG treatment also increased the steady state PRL mRNA levels. This increase was due to an increase in the transcription rate of the gene rather than a decrease in the degradation of PRL transcripts. In summary, we conclude that hCG and LH can increase the morphological as well as functional differentiation of human endometrial stromal cells into decidua. This is one of the newly discovered actions of LH and hCG that may be important for the implantation of blastocyst and maintenance of pregnancy.

Adult↗

Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model.

OBJECTIVE: The purpose of this study was to test the capability of human chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 4 hours before administration of prostaglandin F(2)(alpha), and time to delivery of the first pup was recorded. After initial promising results, mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F(2)(alpha). Delivery times between groups were compared by using the Mann-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride solution on control mice (prostaglandin F(2)(alpha), 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P <.0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment plus prostaglandin F(2)(alpha), 48.5 +/- 20 hours; P <.0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F(2)(alpha) demonstrated significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration did not demonstrate delays in delivery times (P =.46; n = 27). Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F(2)(alpha) on control animals (P <.05; n = 17); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.

Animals↗

Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac.

BACKGROUND & AIMS: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (HRIs) were found incidentally to reduce new cases of colon cancer in 2 large clinical trials evaluating coronary events, although most patients in both treatment and control group were taking nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are associated with reduced colon cancer incidence, predominantly by increasing apoptosis. We showed previously that lovastatin induces apoptosis in colon cancer cells. In the present study we evaluated the potential of combining lovastatin with sulindac for colon cancer chemoprevention. RESULTS: Lovastatin, 10-30 micromol/L, augmented sulindac-induced apoptosis up to 5-fold in 3 colon cancer cell lines. This was prevented by mevalonate (100 micromol/L) or geranylgeranylpyrophosphate (10 micromol/L) but not farnesylpyrophosphate (100 micromol/L), suggesting inhibition of geranylgeranylation of target protein(s) as the predominant mechanism. In an azoxymethane rat model of chemical-induced carcinogenesis, the total number of colonic aberrant crypt foci per animal (control, 161 +/- 11) and the number of foci with 4+ crypts (control, 40 +/- 4.5) decreased to 142 +/- 14 (NS) and 43 +/- 2.9 (NS), respectively, with 50 ppm lovastatin alone; to 137 +/- 5.4 (P = 0.053) and 36 +/- 2.1 (NS) with 80 ppm sulindac alone; and to 116 +/- 8.1 (P = 0.004) and 28 +/- 3.4 (P = 0.02) when 50 ppm lovastatin and 80 ppm sulindac were combined. CONCLUSIONS: Addition of an HRI such as lovastatin may augment chemopreventive effects of NSAIDs or/and may allow lower, less toxic doses of these drugs to be used.

Animals↗

Immortalized hippocampal cells contain functional luteinizing hormone/human chorionic gonadotropin receptors.

We used immortalized HN33p cells as surrogates for hippocampal neurons to investigate the functional importance of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors. The use of various detection techniques demonstrated that HN33p cells contain LH/hCG receptor transcripts and receptor protein that can bind 125I-hCG. Culturing them with highly purified hCG resulted in a significant, although modest, dose-and time-dependent and hormone specific increase in steady state 5-lipoxygenase (5-LO) mRNA and protein levels. The studies on signaling revealed that treatment of HN33p cells with hCG resulted in a robust dose- and a time-dependent significant increase in media cyclic AMP levels. In addition, treatment with a protein kinase (PK)A inhibitor, isoquinolinesulfonamide (H-89), but not with a PKC inhibitor, bisindolylmaleimide (Bis), prevented hCG from increasing the 5-LO protein levels. Pretreatment of HN33p cells for 48 hrs with 2 microM antisense, but not sense, phosphorothioate oligodeoxy-nucleotides (ODN) synthesized from mouse LH/hCG receptor sequence resulted in a dramatic decrease in LH/hCG receptor protein levels. In the antisense, but not in sense, ODN-treated cells, hCG was unable to increase cyclic AMP and 5-LO protein levels, suggesting that receptors are required for hCG to work in HN33p cells.

Animals↗

A toxicity study of simultaneous administration of Tamoxifen and Diazepam to female Wistar rats.

Tamoxifen (TAM) is used in the treatment of breast cancer and decreases the incidence of breast cancer when given to healthy women for different therapeutic purposes. This expansion of its use calls for further studies of its own potential side effects and those in combination with other prescription drugs. Diazepam (DP) is one such drug normally administered to patients who are under cancer treatment and those who suffer from insomnia. The present study examines the effect of individual and simultaneous administration of TAM and DP at therapeutic dose level of 0.8 mg/Kg/day of TAM and 0.3 mg/Kg/day of DP to normal female Wistar rats for a period of 12 weeks. The drugs were administered orally by mixing it in pellet made by wheat dough. There was no significant change in the terminal body weight and liver weights of animals. The ovary weights in TAM + DP treated animals were significantly decreased. The serum succinate dehydrogenase (SDH) levels were significantly lower in TAM, DP and TAM + DP treated rats and comparatively were lowest in TAM and TAM + DP treated animal groups. Serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), acid and alkaline phosphatase (ACP & ALP) levels were significantly higher in the three treated groups, but comparatively lower in TAM + DP treated animals when compared to TAM or DP alone treated rats. There was marked increase in liver triglyceride and cholesterol levels in the three treated groups but remarkable decrease in liver glycogen. Total serum cholesterol levels were significantly high in DP and TAM + DP treated rats and total serum triglyceride levels were significantly high only in TAM treated rats. As a whole it can be concluded that DP does not enhance TAM toxicity on simultaneous administration, but on its own when administered individually brings about perturbation in lipid storage and metabolism.

Administration, Oral↗

Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor.

Inducible nitric oxide synthase (iNOS) is overexpressed in colonic tumors of humans and also in rats treated with a colon carcinogen. iNOS appear to regulate cyclooxygenase-2 (COX-2) expression and production of proinflammatory prostaglandins, which are known to play a key role in colon tumor development. Experiments were designed to study the inhibitory effects of S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT) a selective iNOS-specific inhibitor, measured against formation of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). Beginning at 5 weeks of age, male F344 rats were fed experimental diets containing 0 or 50 p.p.m. of PBIT, or 2000 p.p.m. of curcumin (non-specific iNOS inhibitor). One week later, rats were injected s.c. with AOM (15 mg/kg body wt, once weekly for 2 weeks). At 17 weeks of age, all rats were killed, colons were evaluated for ACF formation and colonic mucosa was assayed for isoforms of COX and NOS activities. Both COX and iNOS activities in colonic mucosa of the AOM-treated rats were significantly induced. Importantly, 50 p.p.m. PBIT suppressed AOM-induced colonic ACF formation to 58% (P < 0.0001) and crypt multiplicity containing four or more crypts per focus to 78% (P < 0.0001); it also suppressed AOM-induced iNOS activity. Curcumin inhibited colonic ACF formation by 45% (P < 0.001). These observations suggest that iNOS may play a key regulatory role in colon carcinogenesis. Developing iNOS-specific inhibitors may provide a selective and safe chemopreventive strategy for colon cancer treatment.

Animals↗

Chemopreventive effect of S-methylmethane thiosulfonate and sulindac administered together during the promotion/progression stages of colon carcinogenesis.

S-methylmethane thiosulfonate (S-MMTS), isolated from cauliflower and having antiproliferative activity, and the non-steroidal anti-inflammatory drug sulindac have been shown to inhibit chemically induced colon carcinogenesis when they are administered during the initiation and/ or post-initiation stages. The present study was designed to investigate the chemopreventive efficacy of 80 p.p.m. S-MMTS administered during the initiation and post-initiation stages and of S-MMTS and sulindac administered together at low doses (40 and 160 p.p.m., respectively) during the promotion/progression phases (late in the premalignant stage) of colon carcinogenesis. At 5 weeks of age, groups of male F344 rats were fed diets containing 0 (control diet) or 80 p.p.m. S-MMTS. At 7 and 8 weeks of age all rats except those in the vehicle-treated groups were given s.c. injections of 15 mg/kg body wt azoxymethane (AOM). Rats receiving the control diet and intended for the study of inhibition of colon carcinogenesis during the promotion/progression phases were continued on the control diet for 14 weeks after the second AOM treatment; they were then switched to experimental diets containing 80 p.p.m. S-MMTS, 160 p.p.m. sulindac or 40 p.p.m. S-MMTS plus 160 p. p.m. sulindac. The rats were maintained on their respective dietary regimens until 52 weeks after carcinogen treatment and were then killed. Colon tumors were evaluated histopathologically. Administration of 80 p.p.m. S-MMTS alone during the initiation and post-initiation stages and promotion/progression stages had no significant effect on colon tumor inhibition. In contrast, the administration of 160 p.p.m. sulindac during the promotion/progression stages did significantly inhibit total colon tumor multiplicity (P < 0.05). Moreover, co-administration of 40 p.p. m. S-MMTS with 160 p.p.m. sulindac during the promotion/progression stages suppressed the incidence and multiplicity of non-invasive adenocarcinomas (P < 0.05-0.01) and multiplicity of invasive and total adenocarcinomas of the colon to a significant degree (P < 0. 05-0.01). These findings have potential clinical implications.

Adenocarcinoma↗

Opioid peptides inhibit the action of oestradiol on human myometrial cells in culture.

The effect of opioid peptides on cultured, oestradiol-stimulated human myometrial cells was examined. Oestradiol increased cell densities in mixed-cell (smooth muscle cells + stromal fibroblasts) cultures by 40%. This oestradiol-induced stimulation of cell proliferation was decreased to control values by D-met2-pro5-enkephalinamide. The half-effective inhibitory concentration of enkephalinamide was 0.3 nmol/l. The opioid-induced inhibition of cell proliferation was blocked completely by the specific opiate receptor antagonist naloxone, while naloxone did not have any effect on its own. This opioid effect was mediated dominantly by the mu opiate receptor. The optimal concentration for oestradiol to stimulate uterine cell proliferation was 2.2 nM. The basal rate of cell proliferation was not affected by enkephalinamide. In saturation experiments, the parameters of specific [3H]-naloxone binding were: dissociation constant = 1.02 nM, maximal binding capacity = 2910 binding sites/cell, Hill coefficient = 1.029. In human myometrial pure smooth muscle cell cultures, oestradiol decreased the proliferation of cells. Progesterone potentiated these oestradiol effects, but had no effect on its own. Enkephalinamide was also able to block the effects of oestradiol, but naloxone did not antagonize it. In summary, here we present a novel inhibitory role of endogenous opioid peptides in the regulation of cell growth and proliferation in the human uterus.

Adult↗

Treatment of human endometrial gland epithelial cells with chorionic gonadotropin/luteinizing hormone increases the expression of the cyclooxygenase-2 gene.

Endometrial glands contain higher levels of LH/hCG receptors than other cells in the human uterus. The present study investigated their functional importance. Northern and Western blotting and covalent receptor cross-linking demonstrated that human endometrial gland epithelial cells in culture contained multiple LH/hCG receptor transcripts and an 80-kDa receptor protein that can bind [125I]hCG in a hormone-specific manner. Culturing cells with highly purified hCG resulted in a time- and dose-dependent increase in steady state levels of cyclooxygenase-2 (COX-2) messenger ribonucleic acid and protein and the secretion of PGE2. Although human LH could mimic hCG, FSH, TSH, and alpha- or beta-subunits of hCG had no effect on COX-2 protein levels. Studies on signaling revealed that treatment of cells with hCG resulted in an increase in cAMP levels and protein kinase A (PKA) activity. Inhibition of PKA activity by cotreatment with isoquinoline-sulfonamide (H-89) prevented hCG from increasing COX-2 protein levels. Treatment with 8-bromo-cAMP mimicked the effect of hCG, and cotreatment with a selective inhibitor of type I PKA, 8-chloro-cAMP, prevented 8-bromo-cAMP and hCG from increasing COX-2 protein levels. The requirement of receptors for LH/hCG action was investigated by 24-h treatment of human endometrial gland epithelial cells with 21-mer phosphorothioate oligodeoxynucleotides (ODNs) synthesized from human receptor sequence. Treatment with 2 micromol/L antisense, but not sense, ODN resulted in a dramatic reduction in LH/hCG receptor protein levels. hCG was unable to increase COX-2 protein, PGE2, and cAMP levels in an antisense, but not in sense, ODN-treated cells. In summary, we conclude that hCG and LH treatment can increase expression of the COX-2 gene in human endometrial gland epithelial cells. The effect was time and dose dependent, hormone specific, and mediated by the cAMP/type I protein kinase A signaling pathway. The hCG actions require a normal complement of its receptors in cells. These hCG and LH effects may be another action of these hormones in human endometrium that is important for implantation of the blastocyst and continuation of pregnancy.

Adult↗

Prevention of colonic preneoplastic lesions by the probiotic Lactobacillus acidophilus NCFMTM in F344 rats.

The experiments described here were aimed at developing novel probiotic strains that may aid in the reduction of colon cancer risk. We assessed the potential anticancer properties of Lactobacillus acidophilus NCFMTM in male F344 rats using inhibition of the formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon as the measure of preventive efficacy. At 6 weeks of age, groups of rats were fed the experimental diets containing 0, 2% or 4% lyophilized cultures of L. acidophilus NCFMTM. At 7 weeks of age, all animals in each dietary group, except the vehicle-treated rats, were s.c. injected with AOM (15 mg/kg body weight) once weekly for two weeks. The vehicle-treated groups were given s.c. injections of normal saline. All rats were necropsied 10 weeks after the last AOM injection and ACF in formalin-fixed, methylene blue-stained colonic tissues were counted under the light microscope. The contents of the cecum were analyzed for bacterial beta-glucuronidase activity. Diet supplementation with the probiotic strain NCFMTM significantly suppressed AOM-induction of colonic ACF, in terms of total number, as well as crypt multiplicity and number of ACF/cm2 colon (P<0.01 - 0.001). NCFMTM inhibited AOM-induced colonic ACF formation in a dose-dependent manner (P<0.01). A significant dose-dependent reduction of cecal beta-glucuronidase activities was observed in the rats fed 2% (P<0.04) and 4% (P<0.0001) NCFMTM. These results suggest that Lactobacillus acidophilus NCFMTM may potentially prevent colon cancer development. Further studies are warranted to determine the full potential of this probiotic strain in preclinical efficacy studies.

Animals↗

Solitary plasmacytoma presenting as peripheral neuropathy: a case report.

We report a 26 year old woman presenting with a chronic predominantly motor radiculoneuropathy. A biopsy proven solitary lytic plasmacytoma was detected in the left sixth rib. Serum immunoelectrophoresis revealed 'M' band (IgG, l light chain). Excision of the plasmacytoma resulted in gradual but steady recovery. We suggest that all patients with 'cryptogenic' polyneuropathy be investigated for this potentially treatable condition. A high index of suspicion assists the organization of appropriate diagnostic investigations.

Adult↗

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents.

Several D-ring modified analogues of podophyllotoxin were prepared viz semi-synthesis starting from naturally occurring podophyllotoxin and determined their in vitro anti-cancer activity. Most of the analogues have shown good activity towards human cancer cell lines.

Antineoplastic Agents↗