Sujoy K. Guha

Phase I clinical trial of an injectable contraceptive for the male

Earlier studies on the rat and the monkey had demonstrated that an injection of styrene maleic anhydride (SMA) in a solvent vehicle of dimethyl sulphoxide (DMSO) into the lumen of the vas deferens is toxicologically safe and has contraceptive action. Phase I clinical trial was therefore undertaken on 38 male volunteers giving varying doses of SMA, ranging between 5 mg and 140 mg, into each vas deferens. A dose of 70 mg is the predicted therapeutic dose based on animal data. That the compound is within the vas deferens lumen during the period of the safety assessment is inferred from the effect on the spermatozoa count in ejaculates which reach azoospermic levels in the higher dose ranges. The treatment is well tolerated with only minimal side effects in a few cases and no long-term adverse effects.

Contraception in male monkeys by intra-vas deferens injection of a pH lowering polymer

A new male method of contraception by injecting a polymer, styrene-maleic anhydride (SMA), into the lumen of the vas deferens has been studied on rhesus monkeys. The polymer has the dual feature that it can occlude the vas deferens lumen and also it can inhibit the fertilising ability of spermatozoa by virtue of the pH lowering effect. Matings with females were carried out when the lumen was completely occluded giving azoospermia as well as with partial block and spermatozoa present in the semen. All matings were infertile. Data up to one year is presented. All indications are that the contraceptive effect will last for a considerably long period.

Reversibility with sodium bicarbonate of styrene maleic anhydride, an intravasal injectable contraceptive, in male rats

A copolymer of styrene and maleic anhydride (SMA) was dissolved in dimethyl sulphoxide (DMSO) and injected into the lumen of the vas deferens of rats. The polymer was retained in the lumen for a period of more than 90 days. Sodium bicarbonate (10%), pH 8.9, was used to flush the polymeric material from the vas deferens lumen. The reversibility and patency of the vas deferens was thus obtained. Sodium bicarbonate proved to be an effective alternative to dimethyl sulphoxide for reversal.

Injectable non-occlusive chemical contraception in the male-I

A new contraceptive technique has been proposed and tested. The method uses a novel polymer which when injected into the vas deferens, lowers the pH sufficiently kill the spermatozoa passing through. The polymer itself does not degrade in the process but can be flushed out to regain fertility. Experiments carried out on rats demonstrate the efficacy of the technique so as to have non-surgical, non-occlusive and reversible male contraception.

Two-year clinical efficacy trial with dose variations of a vas deferens injectable contraceptive for the male

Abstract Contraceptive action of a single intra–vas deferens injection of a specific preparation of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide, forming a drug given the name Risug®, has been demonstrated earlier. Now fertility control over a 2-year period with doses having the SMA component ranging from 40 to 70 mg is reported here. The results suggest that pregnancy protection is obtained both in the azoospermic and non-azoospermic states. Side effects are minimal and transient in nature. Libido remains unaltered.

Potential Biosoluble Carriers: Biocompatibility and Biodegradability of Oxidized Cellulose

The biocompatibility and biodegradability of periodate oxidized cellulose is assessed in vivo. Morophological and histopathological studies over a period of six months indicate that oxidized cellulose degrades slowly without producing excessive tissue reaction. Preliminary investigations on the kinetics of degradation of oxidized cellulose in vitro, immobilization of alpha-chymotrypsin on it and the rate of the enzyme release in a solution of pH 7.4 are also briefly reported.

Effect of a new injectable male contraceptive on the seminal plasma amino acids studied by proton NMR spectroscopy

Effect of RISUG, a newly developed male contraceptive, on various amino acids of seminal plasma ejaculates was studied by proton magnetic resonance spectroscopy at 400 MHz. Levels of amino acids were compared with the seminal plasma of obstructive azoospermia and controls. Glutamic acid, glutamine, and arginine were found to be high in concentration in human seminal plasma. The concentration of aromatic amino acids such as tyrosine, histidine, and phenylalanine in RISUG-injected subjects showed no significant difference compared to controls (p > 0.1); however, there was a statistically significant decrease in the concentration of these amino acids in obstructive azoospermia. The concentration of some prominent amino acids that showed overlapping resonances, such as isoleucine+leucine+valine (p < 0.01), alanine+isoleucine+lysine (p < 0.01), arginine+lysine+leucine (p < 0.01), and glutamic acid+glutamine (p < 0.01), showed a statistically significant decrease in RISUG-injected subjects compared to controls. Overlap of these amino acid resonances were noticed even at 600 MHz. In general, the total amino acids concentration in RISUG-injected subjects was found to be higher than in azoospermic subjects, confirming the occurrence of partial obstructive azoospermia in subjects injected with this contraceptive.

Understanding utero-placental blood flow in normal and hypertensive pregnancy through a mathematical model

Normal development of utero-placental circulation is crucial not only for the survival and growth of the fetus in utero, but also for maternal well-being. Any disturbance or abnormality may reflect underlying pathology. Geometric conversion of a pre-pregnant spiral vessel into a divergent low-resistance vessel is believed to be responsible for the increased utero-placental blood flow in normal pregnancy. Known biomedical investigative techniques have failed to explain many such underlying haemodynamic changes taking place in the utero-placental system. Therefore, proper understanding of the system using a mathematical model has been found to be useful. The physiological fluid dynamic study is the first in this branch of physiology. Abnormal pressure gradient, axial velocity, volume flow and shear rate are obtained for various slowly changing geometries such as, tapering, divergence, local constrictions and sinusoidal tube for low Womersley parameters. The model can explain many enhanced patho-physiological changes, such as persistence or the appearance of local constriction in the utero-placental vessels. Such pathological changes are considered to be responsible for very high utero-placental resistance, leading to blood flow insufficiency in pre-eclampsia or intra-uterine growth retardations. It is believed that these changes may be caused by low shear rate on the pre-existing deranged or abnormal endothelium. Furthermore, this derangement is caused by an abnormal proliferation of either spiral vessels or the invading non-villous trophoblasts. Doppler flow study can explain and validate some of the theoretically derived flow velocity results. The study opens up a new area of research into utero-placental physiological fluid dynamics.

Dynamics of the Ampullary-Isthmic Junction in Rabbit Oviduct

A delay in the ovum transport at the ampullary-isthmic junction (AIJ) has been confirmed by various investigators, but the mechanism of retention and release at this junction is not yet well understood. Using a technique for monitoring unobstructed Fallopian tube motility with an impedance plethysmograph, an increase in luminal diameter was observed at the time when the ova are released from the AIJ. This enlargement persists till all ova emerge from the AIJ. Hence, it seems likely that the AU relaxation is a dominant factor contributing to ova release from the AIJ.

p-Amino salicylic acid — oxidized cellulose system: a model for long term drug delivery

The mobilization of p-amino salicylic acid (PASA) on periodic oxidized cellulose (O.C) as a biocompatible carrier was investigated. The immobilization of the PASA is based on Schiffs base formation between the amino group of PASA and the aldehyde group of O.C. The in vivo and in vitro release of p-amino salicylic acid was studied. Such a system may be useful for the sustained delivery of the drugs in the body, since O.C. itself is a biosoluble carrier.