Indole alkaloids from Muntafara sessilifolia with antiplasmodial and cytotoxic activities

Four vobasinyl-iboga bisindole and one 2-acyl monomeric indole alkaloids were isolated from the stem bark of Muntafara sessilifolia along with eleven known compounds. Their structures and relative stereochemistry were elucidated on the basis of spectroscopic data including 1D and 2D NMR and mass spectrometry (MS). All isolated compounds were evaluated in vitro for antiplasmodial activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum, and for cytotoxicity against the human lung cell line MRC-5 and the rat skeletal muscle cell line L-6. 3'-Oxo-tabernaelegantine A exhibited antiplasmodial activity (4.4 μM IC(50)) associated with non-significant cytotoxicity (selectivity index of 48). Tabernaelegantine B and D displayed the highest cytotoxicity with IC(50) values of 0.47 and 1.89 μM on MRC-5 cells, and 0.42 and 2.7 μM on L-6 cells, respectively.     

Primary hyperparathyroidism: the surgical problems. A study of 1,300 operated patients

In this short presentation the surgical management and then the possible vicissitudes of primary hyperparathyroidism are successively summarized: negative investigations, and the persistence or postoperative recurrence of hyperparathyroidism. Results obtained in a series of 1,300 patients who underwent surgical treatment confirm that a single cervicotomy procedure, without risk for the patient, ensures definitive cure of this disease in 95% of cases.     

Study of a virilizing adrenal cortical tumor. Analysis of urinary steroids by gas-liquid chromatography and mass spectrometry]

The C19 and C21 urinary steroids from a virilizing adrenal tumour with high levels of plasma 17alpha-progesterone and its urinary metabolites have been identified and quantitated by gas chromatography and mass spectrometry of sephadex fractions of the total urinary extract. Of the fifty five identified steroids thirteen were new compounds or known compounds not found before in such a case. The actiology of the apparent 21-steroid hydroxylase deficiency is discussed at the light of these analytical results and of the hormonogenesis enzymatic induction of the tumour biopsy.     

Cutaneous and subcutaneous blood flow during general anaesthesia

The vasodilator effect of anaesthetic agents on cutaneous vessels has often been investigated. In contrast, although subcutaneous tissue is concerned with metabolism and thermoregulation, the effects of anaesthesia on subcutaneous blood flow have not been well documented. The purpose of this study was to determine the magnitude of changes in cutaneous and subcutaneous blood flow during general anaesthesia in Man. Anaesthesia was induced with flunitrazepam in 15 patients before facial plastic surgery. Blood flow was estimated using heat thermal clearance (HC). Two HC sensors in different areas allowed the measurement of superficial and deep HC. Systolic (SABP), diastolic (DABP) and mean arterial blood pressure (MABP), heart rate (HR), and rectal and mean skin temperature were also recorded. After induction of anaesthesia, HR increased significantly (p less than 0.05) whereas SABP, DABP and MABP remained unchanged. The rectal-toe temperature gradient fell from 6.3 +/- 4.1 degrees C to 3.4 +/- 1.1 degrees C (p less than 0.01) suggesting a reduction in vasomotor tone. Superficial HC increased from 0.37 +/- 0.06 to 0.42 +/- 0.08 W.m-1.degrees C-1 (p less than 0.05) whereas deep HC decreased from 0.33 +/- 0.07 to 0.31 +/- 0.09 W.m-1.degrees C-1 (NS) and returned to the control value thereafter. Rectal temperature and mean skin temperature were unchanged. The changes in deep HC are similar to those previously observed in muscle during induction of anaesthesia. Our results show that anaesthesia mainly affects cutaneous blood flow, without any significant change in subcutaneous blood flow during the early phase of anaesthesia in human beings.     

Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans.

The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure (BPa) decreased by 23%-30% and heart rate (fc) increased but only during NTG infusion (+22%; P less than 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: -26%, P less than 0.01; SNP: -34%, P less than 0.02] and subcutaneous vascular resistance changed only with SNP (-31%, P less than 0.02). After hypotension was discontinued the subcutaneous blood flow decreased (-13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between fc and BPa (NTG: r = -0.525, P less than 0.01; SNP: r = -0.622, P less than 0.01) as well as with subcutaneous blood flow (NTG: r = -0.653, P less than 0.001; SNP: r = -0.573, P less than 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W.m-1.degree C-1 vs SNP 0.42 (SEM 0.1) W.m-1.degrees C-1, P less than 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P less than 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects.     

Body coloration and colour alternation among tropical forest mammals

Despite different phylogenetic origins, the mammals of Gabon and Guiana show very similar colour patterns. The coloration is closely correlated with several biological parameters: body weight, diet, and activity rhythm. The less dangerous the living conditions, the more easily perceptible are body colours. Within the same community, the degree of colour convergence between species of similar body size is very low among diurnal carnivores or between they and their prey, that is when interspecific encounters can be dangerous. In contrast, it is higher among diurnal terrestrial frugivores or folivores of similar size, than among those of unequal size. Owing to the few colours available, and to the regular size spacing between species, all species are arranged into narrow unicoloured size strata (indistinct colour or red), regularly alternating along the whole size range. Since most species of similar size are well differentiated from each other by ecology, each solitary animal can be sure that another having both the same size and colour is conspecific. The colour alternation does not exist when it is not useful: nocturnal, arboreal, or flying mammals.     

The process of total tail autotomy in the South-American rodent, Proechimys

Tail autotomy in Proechimys cuvieri was studied both morphologically and histologically. The rupture always occurs at the base of the external tail, e.g. in the immediate vicinity of its junction with the body. It thus concerns the whole caudal appendage. The distal epiphysis is separated from the fifth caudal vertebra and lost with the rest of the tail. There is no single reason responsible for the constancy of this breaking point, but several morphological factors can act together: these include strong binding of the five first caudal vertebrae to the body, disappearance of the plurisegmental muscles beyond this level, and the great extent and loose structure of the epiphyseal plates. Autotomy is a biological event occurring throughout the life of the animals, but it is of a cumulative nature. Tail loss is much more prevalent in older and heavier animals than in juveniles. Overall, about 9% of wild populations show this loss. Owing to the increasing percentage of occurrence from young to old, tail autotomy seems to enhance the survival chances of its owner, although direct proof of any predation influence are still lacking.     

Differential expression of dipeptidyl peptidase IV in human versus cynomolgus monkey skin eccrine sweat glands

Dipeptidyl peptidase IV (DPP4) is a peptidase whose inhibition is beneficial in Type II diabetes treatment. Several evidences suggest potential implication of DPP4 in skin disorders such as psoriasis, keloids and fibrotic skin diseases where its inhibition could also be beneficial. DPP4 expression in human skin was described mainly in dermal fibroblasts and a subset of keratinocytes in the basal layer. Of importance in the perspective of preclinical experimentation, DPP4 distribution in skin of non-human primate species has not been documented. This report evidences unexpected differences between a set of human and cynomolgus monkey skin samples revealing a major expression of DPP4 in eccrine sweat glands of cynomolgus monkeys but not in humans. This represents a unique distinctive feature compared to the conserved expression of dipeptidyl peptidases 8 and 9 and potential relevant DPP4 substrates such as neuropeptide Y (NPY) and receptors (NPY-receptor 1 and Neurokinin receptor). Finally the observation that cathepsin D, an unrelated protease, shows the opposite expression compared to DPP4 (present in human but not in cynomolgus monkey eccrine sweat glands) could indicate that human eccrine sweat glands evolved a divergent protease repertoire compared to non-human primates. These unexpected differences in the eccrine sweat glands protease repertoire will need to be confirmed extending the analysis to a major number of donors but could imply possible biochemical divergences, reflecting the functional evolution of the glands and the control of their activity. Our findings also demonstrate that non-human primates studies aiming at understanding DPP4 function in skin biology are not readily translatable to human.