Stainless steel electrodes were chronically implanted through the right facial canal of 30 guinea pigs, close to the potential generator (VIII nerve). Compound action potential (CAP) thresholds, N1 latencies and input-output curves were recorded on day of implantation and 2, 4 and 8-12 weeks later. In the same sitting, auditory evoked brain stem response (ABR) thresholds, latencies and inter-peak-latencies were measured on both sides as a control. N1 thresholds and latencies at low and high intensities were stable. N1 amplitudes, however, showed some variation. Rate of infection was low and reimplantation was successful. Preserving the facial nerve as a land mark was found advantageous, particularly on reimplantation, and did not affect the CAP recording. The technique, originally described by Hildesheimer et al., proved to be reproducible. A few technical difficulties are pointed out and the implication of some interesting findings are discussed.

Animals↗

PubMedDate not supplied

Synthesis and study of the antischistosomal potency and induced biological parameters of a new 2-palmitoyl analogue of the universal antihelminthic praziquantel.

2-Palmitoyl[1,2,3,6,7,11b]hexahydro-4H-pyrazino[2-la]isoquinoline-4-one [III] a highly lipophilic analogue of the universal antihelminthic PRAZIQUANTEL [I] was rationally multi-stepwise synthesized and antischistosomally and biochemically screened. The 2-palmitoyl conjugation was hypothesized to be an antischistosomal adjuvant (Tween 40 mimicry), to the reported crucial pyrazino-isoquinoline moiety. On a constant weight doses bases of I and III (500 mg/kg mouse body weight), the activity of III was found to be approximately 70% of I (mice infected with S. mansoni cercariae) and with satisfactory toxicological and biochemical profile (mice liver and kidney functions). Equivalent molar weight assay (M 1:1.4 for I and III, respectively), which could further plead in favour of the potency of III, was not yet tested. The analogue III, which favourable incorporates the human metabolically and physiologically compatible, palmitic acid segment, seems to be an antischistosomally promising candidate for more integrated studies.

Animals↗

PubMedDate not supplied

Synthetic and bioorganic investigations of 2-cyclohexylthiocarbonyl( 1,2,3,6,7,11B)hexahydro-4H-pyrazino [2-1a] isoquinoline-4-thione, a new dithione mimic of the universal anthelminthic Praziquantel.

As a continuation for our previous approaches to establish structure-antischistosomal activity relationship (SAR) among some new rationally synthesized analogues of praziquantel, herein a new C-4 and C-12 dithione mimic of the drug namely, 2-cyclohexylthiocarbonyl (1, 2, 3, 6, 7, 11b) hexahydro-4H-pyrazino[2-la]isoquinoline-4-thione (II) was synthesized and antischistosomally investigated (mice infected with S. masoni cercariae). Further, some significant biochemical and toxicological parameters for both the control and the dithione II treated mice, particularly the total serum and liver proteins, liver enzymes, serum total lipids, cholesterol, triglycerides, albumin, globulins and creatinine, were assayed. The determined induced amino acid profile of liver protein hydrolysate could indicate a close similarity of the working biological mechanism for both I and II. Comparable to praziquantel, the dithione II was found, still promisingly antischistosomally active (approximately 70% of I, collective average activity, based on 500 mg II/kg mouse body weight). Equally, generally tolerant toxicity parameters for liver and kidney functions could be attributed. Due to the still absence of quasi-potent praziquantel candidates since its discovery (1975), the dithione II could be considered as an interesting anthelminthic candidate susceptible for further profound studies and structure modulations. In this context, some perspectives were also suggested.

Animals↗

PubMedDate not supplied

Synthesis of a new antischistosomally active and toxicologically tolerant C-12 monothione surrogate of the universal antihelmintic praziquantel.

A new C-12 monothione mimic (III) of the universal antihelmintic Praziquantel (I) namely, 2-cyclohexylthiocarbonyl( 1,2.3,6,7,11b)-hexahydro-4H-pyrazino[2-1a] isoquinoline-4-one was chemically synthesized and structurally elucidated (Elemental analysis. El-Mass, 13C-NMR and IR spectroscopy). Antischistosomal potency in the order of -76% comparable to that for our newly reported C-12 and C-4 dithion mimic II (-70%) and Praziquantel. Praziquantel (100%, mice infected with S. mansoni cercariae), was realized. Toxicological evaluation (mice liver and kidney functions) and biochemical parameters (cholesterol, triglycerides, albumin, total serum proteins and amino acid profile of liver protein homogenate) were also assayed. Comparable to the parent drug, general insignificant toxicological diferences could be attributed for III. Interestingly, III exhibited intermediate biological figures between I and II. An order of II III>I, for the other tested biochemical parameters was observed. A consideration of obtained results could indicate that, structurally, an intact glycine amide segment of the pyrazine moiety, as it is the case in both I and III, and not in II (glycine thioamide) seemed now more crucial for exhibiting an optimum antihelmintic potency as well as a more tolerant toxicity characteristics. Additionally, the obtained comparable amino acid profile of mice liver protein homogenate after the treatment by III, could suggest similar biochemical, lethal mechanistic and metabolic routes for II, III and I. The new lipophilic candidatee III seems to merit more profound chemical, biological, and pharmaceutical investigations.

Animals↗

PubMedDate not supplied

Decreasing the number of points in the standard curve for determining iron in flour: summary of collaborative study.

Seven laboratories participated in a collaborative study conducted to (1) evaluate the effects of reducing the number of points for the standard curve in the AOAC Official Method for iron in flour 944.02A-944.02C(a) from 10 points to 5 points, and (2) compare the levels of iron found in foods by using the 10-point and 5-point standard curves. The 5 points (0.2, 0.6, 1.0, 1.4, and 1.8 micrograms Fe/mL) were selected by eliminating every other standard point from the 10-point curve after correction for the reagent blank. No differences in the performance parameters between method versions were found when blind duplicate analysis was used to estimate the performance parameters for each sample analyzed. Results from 2 laboratories were excluded from statistical calculations because of failure to follow the specific instructions to increase the dilution when sample absorbance readings exceeded the highest standard point reading. The 5-point standard curve has been adopted first action in method 944.02 by AOAC INTERNATIONAL.

Flour↗