Prolactin response to metoclopramide does not distinguish patients with hypogonadotrophic hypogonadism from delayed puberty.

The prolactin response to metoclopramide (MCP) was studied in 23 sexually immature males, 14 with isolated hypogonadotrophic hypogonadism (IHH) and nine with constitutional delayed puberty. Six of the 14 IHH patients had not been treated prior to our study, whereas eight had received long term therapy with testosterone or hCG for variable periods ranging from 1 to 20 years. We also measured the prolactin response to chlorpromazine (CPZ) in the untreated IHH men. In these untreated subjects, we observed a greatly diminished prolactin response after CPZ by comparison to that measured following MCP administration (peak 15 ng/ml, areas 86 units vs peak 43 ng/ml, area 416 units, respectively) (P less than 0.01). Furthermore, prolactin levels following MCP were similar in untreated (peak 43 ng/ml, area 416 units) and treated (peak 55 ng/ml, area 545 units, NS) IHH males as well as in boys with constitutional delayed puberty (peak 50 ng/ml, area 532 units, NS). In addition, responses in the three groups of patients were about half (P less than 0.01) those measured in normal men (peak 81 ng/ml, area 845 units). These data indicate that, unlike CPZ, MCP is not useful in distinguishing patients with hypogonadotrophic hypogonadism from boys with constitutional delayed puberty.

Prostaglandins and cellular reaction in uterine flushings. I. Effect of IUD insertion.

Uterine prostaglandin (PG) levels and cellular reaction in response to IUDs were elevated in sixty women. Short-term users (n = 30) were studied in a control cycle and 3 months after IUD insertion, and long-term users (n = 30) were studied at least 2 years after device insertion. A uterine wash was performed in the proliferative and luteal phase of each investigated menstrual cycle; the cellular components were counted and levels of PGE2, PGF2 alpha and their 13,14-dihydro-15-keto metabolites measured. A significant rise in PG levels was observed in the uterine wash shortly after IUD insertion, particularly in the luteal phase. However, there was a significant reduction in PG levels among long-term users, though the cellular reaction showed a continued increment. The absence of correlation between the biochemical and biological responses indicated that neither of them was totally dependent on the other. The decreased PG levels among long-term users does not support the concept of a key role for these substances in the mechanism of action of IUDs. The temporary post-insertion rise in PG levels coincides with the phase of increased bleeding and pain.

Prostaglandins and cellular reaction in uterine flushings. II. Effect of PG synthesis inhibition in IUD users.

The effect of oral administration of indomethacin (100 mg/day), a potent inhibitor of prostaglandin (PG) biosynthesis, on the PG levels and cellular profile in the uterine flushings in response to the use of an IUD (Lippes Loop size C) was studied in sixty women. Indomethacin reduced the cell counts in both follicular and luteal phases of menstrual cycles before and after IUD insertion. The anti-inflammatory drug decreased PGE2 and PGF2 alpha levels in both phases of the cycle before IUD insertion. After insertion, it inhibited only the formation of PGF2 alpha and its 13,14-dihydro-15-keto metabolite in the luteal phase but not in the follicular phase. In long-term users, however, the drugs reduced the levels of all PGs studied in the luteal phase and only PGF2 alpha and its metabolite in the follicular phase. The implications of these findings in the mechanisms of contraceptive action of IUDs and their side effects are discussed.

Effect of some additives on the properties of phenazopyridine hydrochloride granules and their corresponding tablets.

The effect of the diluents, lactose and calcium carbonate and of the binders, syrup, gelatin, methylcellulose and Eudragit E on the physical properties of phenazopyridine hydrochloride (PNHCl) granules was evaluated. A correlation existed between the granules' physical properties and those of their compressed tablets. With regard to drug release, lactose-syrup 30% was the best of all diluent-binder combinations, followed by lactose-methylcellulose 4%. Also lactose was found to be superior to calcium carbonate in drug release when gelatin and methylcellulose were used as binders. Eudragit E was the best binder with calcium carbonate in this respect. On the other hand, the bioavailability of PNHCl in humans was the same when lactose was used with either gelatin, syrup or methylcellulose, but higher than that obtained with a combination of calcium carbonate and Eudragit E 15%.

Simultaneous solubility and dissolution rate of sulfamethoxazole and trimethoprim in binary mixture.

The solubilities of trimethoprim in solutions with different pH values decreased in the presence of sulfamethoxazole, while that of the latter increased in the presence of the first. The dissolution rate of trimethoprim in HCl (0.1 mol/1) was the same in the presence and absence of sulfamethoxazole. That of sulfamethoxazole however, decreased in the presence of trimethoprim. The different reasons were explained.

The use of directly compressible vehicles for the preparation of vitamin B1 tablets.

The classical method for the preparation of vitamin B1 tablets led to tablets of doubtful and/or shorter stability. Dipac , Emdex , Nu-Tab and Sugartab , were evaluated as direct compression vehicles for the preparation of vitamin B1 tablets. Avicel was also employed as a traditional vehicle for comparison. These vehicles were evaluated at different concentrations compared with vitamin B1 tablets available in the Egyptian market and prepared by the classical method. Generally, it was found that increasing the concentration of the vehicles in the tested vitamin B1 formulations improved the physical standards and mechanical strength of the tablets produced. Avicel was found to be the most suitable vehicle, followed by Dipac and Emdex . However, Sugartab and Nu-Tab were found to be the worst in this respect.

Neural regulation of pancreatic polypeptide release.

To clarify the nervous system's role in the regulation of pancreatic polypeptide (PP) release, extrinsic innervation to the in situ pancreas was eliminated in five dogs. Before and 2 weeks after denervation, PP was measured during insulin hypoglycemia and ingestion of a protein meal. Exogenous insulin caused a similar marked hypoglycemia in both control and denervated dogs. Hypoglycemia caused a significant increase in plasma PP in control dogs from a baseline of 42 +/- 8 pg/ml to 86 +/- 18 pg/ml at 20 minutes (P less than 0.01). In denervated dogs plasma PP did not increase with hypoglycemia, and levels were significantly less than in the control animals at 30 and 60 minutes (P less than 0.05). With a protein meal, PP increased in the control animals from 53 +/- 12 to 116 +/- 16 pg/ml at 10 minutes (P less than 0.05), 164 +/- 22 pg/ml at 20 minutes (P less than 0.05), and 193 +/- 20 pg/ml at 60 minutes (P less than 0.01). Denervation markedly blunted this response, and PP increased only from 53 +/- 6 to 64 +/- 4 pg/ml at 10 minutes, to 83 +/- 12 pg/ml at 20 minutes, and to 91 +/- 8 pg/ml at 60 minutes. PP became significantly elevated above baseline in denervated dogs only at 60 minutes (P less than 0.05), and PP was significantly lower than in the control group at 10, 20, and 60 minutes after the meal (P less than 0.05). Immunostaining for insulin, glucagon, somatostatin, and PP showed no difference in the number and distribution of these endocrine cells in predenervation and postdenervation specimens. Adrenergic and cholinergic nerves were seen in all control specimens but, except for a few adrenergic fibers, were not seen in denervated animals. Peptidergic nerves that contained vasoactive intestinal polypeptide (VIP) were seen in all areas of the pancreas before and after denervation. This study confirms that the initial rise in PP with a protein meal is governed by vagal cholinergic pathways. Later postprandial PP secretion is controlled by an interplay between these cholinergic pathways and other uncertain influences such as hormonal or substrate changes. The pancreas has a rich intrinsic peptidergic system of VIP-containing nerves.

Simultaneous in vitro and in vivo evaluation of both trimethoprim and sulfamethoxazole from certain dosage forms.

The dissolution rates of trimethoprim (T), and sulphamethoxazole (S), from different brands of tablets and suspensions were studied at pH = 1.1 and 7.2. The bioavailabilities of both drugs in humans were studied by the urine excretion method. The dissolution rates were dependent on the pH of the dissolution medium, the solubilities of the drugs at the pH involved, the dosage form and the brand studied. While the dissolution rates of T from all brands studied were consistent with their pH-dependent solubility, those of S were not. The dissolution rates of S from suspensions were found to be equal at pH = 7.2, but different at pH = 1.1. A correlation existed between the dissolution rate of T at pH = 1.1 from tablets and the excretion rate in humans. With S, however, no such correlation was observed at either pH.

Use of a fractional factorial design to evaluate granulations prepared in a fluidized bed.

Sulfadiazine granules were prepared in a fluidized bed granulator. The granulation conditions such as binder concentration, velocity and temperature of fluidizing air, pressure of compressed air and binder solution flow rate were studied at two levels, low and high. By applying fractional factorial design the effect of these granulation conditions as well as the interaction among them, on the granules physical characters were assessed.

Influence of intravenous pirenzepine on gastric acid and pepsin in man.

Patients with dyspepsia were asked to volunteer for two gastric secretion tests preceded by a single intravenous injection of pirenzepine 10 mg in the one and 0.9% saline in the other (in random order). In each test gastric secretion was aspirated continuously. 0.9% saline was infused intravenously for 30 minutes followed by insulin 0.15 micrograms/kg-h for 90 minutes, saline for 30 minutes and finally pentagastrin for 90 minutes in doses of either 6, 1, 0.5 or 0.25 micrograms/kg-h. Gastric samples were analysed for volume, pH, titratable acidity and pepsin. Basal outputs of acid and pepsin were not altered by pirenzepine. Insulin-stimulated acid output was significantly reduced (p less than 0.05) from a mean of 32.7 to 22.6 mmol/h (-31%). The mean percentage reduction was 16%. Acid and pepsin outputs after pentagastrin 0.25-6 micrograms/kg-h were not significantly altered by this dose of pirenzepine.

The effect of pirenzepine on meal-stimulated gastrointestinal hormones.

The effects of pirenzepine on the plasma concentrations of gut hormones in the fasting and postprandial states were studied in six healthy subjects. On separate days and in random order, 10 mg pirenzepine, in 2 ml of solvent, or 2 ml saline (0.15 mol/l) were given intravenously 30 min before a standard normal breakfast (2220 kJ). Pirenzepine was not found to affect basal or postprandial levels of insulin, glucagon, gastric inhibitory peptide (GIP), neurotensin, vasoactive intestinal peptide (VIP) or somatostatin. The basal concentration of pancreatic polypeptide (PP) was lowered (p less than 0.05) and the postprandial elevation reduced, though not significantly. While the basal concentration of motilin was also suppressed (p less than 0.05), the postprandial elevation remained unchanged following pirenzepine. The release of enteroglucagon was reduced significantly in the basal and postprandial states (p less than 0.05 and p less than 0.025 respectively). The postprandial gastrin response was prolonged slightly, but insignificantly, by pirenzepine. It is concluded that pirenzepine does not exert any major or unexpected actions on the hormonal control of digestion.

Stability of indomethacin solubilized system.

Physical and chemical stability testing was carried out for indomethacin in the form of solution, syrup and elixir solubilized by Tween 80 and Brij 99. It was found that sucrose and alcohol markedly stabilize the indomethacin solution.

The effect of a second laminated gelatin film on the release rate of sulfadiazine from gelatin-gel matrix.

The influence of a second laminated gelatin film without the drug over a gelatin-gel matrix containing sulfadiazine on the release rate was investigated. It was found that increasing the thickness of the second laminated layer markedly decreased the release of the drug incorporated in the gelatin layer.

Solubilization of indometacin.

Three methods were employed for the solubilization of indometacin as an example of antirheumatic drugs, employing:--Non-ionic surface-active agents such as Tween 80 and 40, Myrj 53 and Brij 99,--urea and sodium citrate--urea-indometacin coprecipitate. The solubility of indometacin by nonionic surface active agents was in the following order: Tween 80 and Brij 99 greater than Tween 40 greater than Myrj 53. The efficiency of solubilization by these surfactants decreased as the polyoxyethylene chain increased. Urea increases the solubility of indometacin due to enhancing the solvation of the drug by water. Up to a concentration of 0.2 M sodium citrate increases the solubility of indometacin, followed by a sharp decline in the solubility by increasing its concentration of sodium citrate. Urea-indometacin coprecipitate show slight increase in the solubility of the drug.

Effect of liquid additives on release of chloramphenicol from ointment bases.

1, 3 and 5% water, ethyl alcohol, glycerol and propylene glycol were incorporated into oleaginous, absorption, emulsion (O/W and W/O) and water-soluble ointment bases (resp.) containing 5% of chloramphenicol and diffusion rate via the dialysis method was measured for 2 h. The rate of release was found to be greater from water-soluble bases than from the other bases, since rates from oleaginous, absorption and W/O emulsion bases were found to be the least in this respect. The effect of liquids added to these bases on drug release was found to be less pronounced than that obtained with water-soluble and O/W emulsion bases. For O/W emulsion bases the addition of ethyl alcohol increased the release of chloramphenicol as its concentration was increased. Propylene glycol increased the release at a concentration of 3%, but higher concentration produced opposite results. Glycerol was found to have a little effect in 5% concentration, but it increased the release as the concentration dropped to 3% concentration.