Evaluation of beta-tethymustine, a new anticancer compound, in murine tumour models

beta-Tethymustine, 1-[2- {bis(2'-chloroethyl)amino}ethyl]spiro[imidazolidine-4,2'-(1'H),3',4'-dihydronaphthalene]-2,5-dione, has been synthesised and LD50 value determined in Swiss male mice, which was found to be 100.00 mg/kg by single i.p. injection. The following three criteria, namely ascites cell count, ascites fluid measurement and increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice, were studied for evaluation of its antitumour efficacy in vivo in three murine ascites tumours, namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). At the optimum dose range of 8.0 mg/kg (higher) to 4.0 mg/kg (lower) for 1-7 days treatment following tumour transplantation on day 0, it exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and displayed excellent ILS(max) value of 80 in EAC, 224 in S-180 and 240 in DL, respectively, showing 'curative' effect (2-3/6 mice having 90 days survival rate). It also demonstrated a high ILS value of 150 with one cure/six mice bearing S-180 for 6 days prior to drug therapy. Screening results were compared with two clinical drugs, cyclophosphamide and 5-fluorouracil, serving as positive controls. Its chemical alkylating activity was compared with nor-HN2 (NSC 10873) and spiromustine (NSC 172112). The results indicate that it possesses greater alkylating activity than nor-HN2 and comparable activity with spiromustine.     

Hormones in male-patients with advanced esophageal-carcinoma

Hormones are believed to play a dominant role as promoters in the growth and development of hormone-dependent cancers. Much less is known about the circulating hormones in male patients with oesophageal cancer. This lack of attention led us to evaluate the role of peptide and steroid hormones (by RIA) in male patients with oesophageal cancer (n=49). Blood samples of patients were collected pretherapeutically and data was compared with age matched controls (n=25). In this retrospective study, significantly high levels of FSH (P<0.02), LH (P<0.001) and prolactin (P<0.001) were observed with concomitant low levels of estradiol (P<0.001), DHEA-S (P<0.02) and testosterone (P<0.001) in patients when compared with respective controls. The patients when grouped according to anatomical site and histological type of the tumor, intergroup variation was not observed in these hormones. From our, study, it seems that hormonal imbalance or altered ratio of peptide and steroid hormones might be playing a significant role in the development and/or progression of oesophageal carcinoma in men.     

Embryonal Rhabdomyosarcoma of tympano-mastoid region

A rare case of Embryonal Rhabdomyosarcoma of the tympanomastoid region with paralysis of VIth and VIIth cranial nerve and development of ipsilateral loss of vision is reported. The case was first clinically diagnosed as a complicated case of C.S.O.M. with petrositis and facial palsy and was operated upon. Histopathological examination in the postoperative period proved it to be a case of Embryonal Rhabdomyosarcoma.     

Congenital anomaly of the toes, microophthalmos and haemangioma

A two-and-half month-old female infant with cavernous haemangioma, agenesis and syndactyly of toes, microophthalmia and microcornea is reported.     

Life cycle of maternal health and child health

This editorial presents data on maternal and child health and mortality in India. Since 1946, government health recommendations have recognized the high rate of mortality affecting women and children as well as the extent of malnutrition and disease they suffer. The Eighth Five-Year Plan has set specific goals for the years 2000 in terms of the infant, under age five years, and maternal mortality rate; the crude birth and death rates; life expectancy; elimination of poliomyelitis and neonatal tetanus; immunization coverage; and delivery by trained attendant. A discussion of recent data reveals that only slow declines have occurred in neonatal mortality and that a significantly higher age specific death rate for 0-4 years exists in rural than in urban areas. Malnutrition is shown to affect nearly half of all children and to contribute to 60% of all child deaths. Irrational drug use is also a major health problem. The family planning program has been burdened with targets and has focused on sterilization in women over age 35. This approach has had little effect on the birth rate. Tabulation of the relationship between birth rate, infant mortality rate, and marriage age shows the importance of marriage age. A table also illustrates the percentage of births by type of attendant in rural and urban areas. The low status of women is seen as contributing to the problem, with females having a higher death rate than males until age 35. While these statistics are pessimistic, some organizations are producing excellent work in an effort to solve these problems.     

Immunohistochemical localization of receptors for progesterone and oestradiol-17 beta in the implantation site of the rhesus monkey

The aim of the present study was to examine the cellular basis of the involvement of oestradiol and progesterone in blastocyst implantation in the primate. To this end, the cellular distribution of receptors for oestradiol (ER) and progesterone (PR) in fetal trophoblast cells and in endometrial compartments of timed lacunar (pre-villous) and villous stages of placentation in primary implantation sites collected on days 13-22 of gestation were investigated in rhesus monkeys. Both in pre-villous stage tissue and in villous stage tissue, cytotrophoblast cells and syncytiotrophoblast cells and other trophoblast derived cells were PR positive, while they were generally ER negative. Maternal endometrial cells were ER negative, while epithelial cells, stromal cells and vascular endothelial cells in maternal endometrium showed heterogeneous staining patterns for PR depending on their relative location; these patterns, however, correlated well with glandular hyperplasia and differentiation, stromal-decidual transformation and vascular response seen during blastocyst implantation.     

Analysis of two types of cone bipolar cells in the retina of a New World monkey, the marmoset, Callithrix jacchus.

Two types of cone bipolar cells, the blue cone bipolar cell and the diffuse bipolar cell (DB3), were labelled immunohistochemically and investigated in the retina of a New World monkey, the marmoset. Blue cone bipolar cells were labelled with an antiserum against cholecystokinin. Short-wavelength-sensitive (SWS) cones were labelled with an antiserum against the SWS cone opsin. The DB3 cells were labelled with antibodies to calbindin. Blue cone bipolar cells in marmoset do not form a regular mosaic but instead follow the random distribution of the SWS cones. Nevertheless, the SWS cone to blue cone bipolar cell connectivity in marmoset is very similar to that previously described for macaque. In contrast to the blue cone bipolar cells, the DB3 cells form a regular mosaic. The synaptic connectivity of DB3 cells in the inner plexiform layer was analyzed. They make output synapses onto ganglion cells and amacrine cells, and gap junctions with each other. Our results provide further evidence for the existence of parallel bipolar cell pathways in the primate retina and support the view that the retinae of Old World and New World primates have common neuronal connectivity. The random distribution of SWS cones and blue cone bipolar cells is an exception to the general rule of a regular mosaic distribution of cell populations in the retina.     

Midget and parasol ganglion cells of the primate retina express the alpha1 subunit of the glycine receptor

Glycine is a major inhibitory neurotransmitter in the mammalian retina and has been shown to influence the responses of ganglion cells. Midget and parasol ganglion cells serve distinct physiological roles in the primate retina and show differences in their response characteristics to light stimuli. In the present study, we addressed the question of whether the expression of glycine receptors differs in midget and parasol ganglion cells. Ganglion cells in the retinae of marmoset and macaque monkeys were injected with Neurobiotin in a live in vitro retinal whole-mount preparation. Retinal pieces were then processed with an antibody against the alpha1 subunit of the glycine receptor. Strong punctate immunoreactivity indicative of synaptic localization is present in the ON and OFF sublamina of the inner plexiform layer. Many of the immunoreactive puncta coincide with the dendrites of both midget and parasol ganglion cells. Immunoreactive puncta are present on distal and proximal dendrites of ON and OFF cells. These results suggest that ON and OFF midget and parasol cells do not differ with respect to the distribution of the alpha1 subunit of the glycine receptor.     

Immunohistological localisation of vascular endothelial growth factor in human endometrium.

Several polypeptide growth factors regulate epithelial and stromal development in endometrium under the influence of estrogen and progesterone, and thereby regulate growth and differentiation of endometrium during menstrual cycle. However, little is known about the angiogenic growth factors that may affect endometrial vasculature throughout each menstrual cycle. Vascular endothelial growth factor (VEGF) is suggestively an important angiogenic growth factor in the female reproductive tract. The aim of the present study was to immunolocalize and assess semi-quantitatively VEGF immunostaining in cells of proliferative phase (n = 3), secretory phase (n = 6) and hyperplastic (n = 6) human endometrial samples. VEGF concentrations were significantly higher in glandular (P < 0.001) and stromal (P < 0.01) compartments of proliferative stage endometrium compared with those in secretory stage and hyperplastic endometrial samples, with no difference in the scores for glandular and stromal compartments between secretory stage and hyperplastic endometrial samples. Generally, glandular expression of VEGF was higher as compared to stromal compartment. Thus, it appears that endometrial VEGF expression and concentration are enhanced by estrogen, and may be correlated with neovascularization and increased vascular permeability during late proliferative period. Additionally, there was no enhancement in VEGF expression in hyperplastic glands, suggesting that regulation of glandular growth and that of angiogenesis in human endometrium operate through different mechanisms.