Reproductive Study of Acrolein on Two Generations of Rats

Four groups of 30 male and 30 female rats were intubated with70 daily doses of acrolein at levels of 0, 1, 3, or 6 mg/kgin a dosing volume of 5 ml/kg. Rats within each dosing group(F₀ generation) were then assigned to a 21-day period of cohabitationand dosing for females continued through cohabitation gestationand lactation. Males were euthanized after cohabitation. F₁generation rats were chosen from pups, and a similar pretreatment,cohabitation, gestation, and lactation regimen was accomplishedresulting in F₂ generation pups. Reproductive parameters, bodyweights, food consumption, and clinical signs were recordedand necropsies were carried out on all treated animals. Histopathologicexams were accomplished on selected reproductive tissues. Inaddition, gross lesions, target tissues, stomachs, and lungswere examined. For the most part, reproductive parameters wereunaffected by acrolein treatment with the exception of reducedpup weights in the F₁ generation pups at the high-dose level(6 mg/kg/day). Gastric lesions were noted consistently in high-doseanimals and some mid-dose (3 mg/kg/day) rats. Erosions of glandularmucosa and hyperplasia/hyper keratosis of the forestomach werethe most frequent stomach lesions observed. Effects on bodyweight gains were noted frequently for the high-dose animalsand achieved statistical sig nificance in the mid-dose animalson several occasions. Mortality in all high-dose animals waselevated relative to control animals. Acrolein, therefore, cannotbe considered a selective reproductive toxin in the rat, butdoes produce toxicological effects down to a dosing level of3 mg/kg/day.     

Studies on the Erythropoiesis Inhibiting Factor in the Plasma of Animals with Transfusion Polycythemia

Further investigations of the action of polycythemic plasma filtrate were madeusing Fe⁵⁹ and with detailed examination of the blood and bone marrow. Thesestudies confirmed the appearance of an active thermostabile plasma factor(erythropoiesis inhibitor) which depressed erythropoiesis in normal rabbits orrats. The plasma obtained from bilaterally nephrectomized sheep subjectedto transfusion polycythemia also contained the erythropoiesis inhibitor. Blockade of the reticuloendothelial system using trypan blue, in sheep, inducedproduction of the active substance similar or identical with the erythropoiesisinhibitor produced after transfusion polycythemia.

Submitted on November 2, 1960 Accepted on October 10, 1961     

The Importance of Decalcification in the Treatment of Tuberculosis I. The Influence of Decalcification in the Course of Healing in Experimental Tuberculosis in Guinea pigs1

The authors have the opinion that hypercalcification of the morbid pulmonary tissue in destructive pulmonary tuberculosis impedes the requisite penetration by the therapeutic agents employed. Experiments were made on guinea pigs, one group receiving antibiotics together with chemical compounds of the EDTA type having a decalcifying effect, while a second group received calcifying agents as well as therapeutic drugs. For control, a third group was treated solely with streptomycin and isoniazid. Chemical, anatomicopathological and histopathological tests provided criteria for evaluation. The best therapeutic results were obtained in the group of decalcified animals.     

ASSESSMENT OF DIAZEPAM LOADING DOSE THERAPY OF DELIRIUM TREMENS

The efficacy of the diazepam loading dose method of treatmentof delirium tremens was assessed in comparison with the traditionaltherapy. The experimental group and the control group comprised51 and 45 patients respectively. The clinical institute withdrawalassessment for alcohol (CIWA-A) scale was applied to assessthe intensity of the symptoms. Diazepam doses in the experimentalgroup oscillated from 40 to 210 mg (mean 86.9±47.2 mg).The control group was receiving diazepam and other psychotropicdrugs in divided doses. In the experimental group deliric symptomswere present from 2 to 24 h (mean 6.9±4.8 h), and inthe control group from 2 to 123 h (mean 33.8±25.7 h).The results show a large efficacy of the loading dose methodcorresponding to substantial reduction of the psychosis duration(fivefold in comparison to the control group). The method provedto be safe, with no significant complications.     

NEUROPEPTIDES IN PSORIASIS: POSSIBLE ROLE OF BETA-ENDORPHIN IN THE PATHOMECHANISM OF THE DISEASE

Background. An increased concentration of neuropeptides in psoriatic lesional skin may be responsible for alterations in the neurogenic erythematous response and transmission of stimuli through sensory nerve fibers (sensation of pruritus). Methods. Increasing doses of capsaicin from 0.125 to 4 μg/ cm² were applied to nonlesional psoriatic skin to establish the minimal dose that induced the substance P-mediated neurogenic response in 30 patients with psoriasis. Plasma beta-endorphin was quantitated in 71 psoriatics by radioimmunoassay using NEN 1251-RIA kit. Results. The mean beta-endorphin concentration was increased about 2-fold compared to normals, whereas doses of capsaicin needed to induce erythema were higher (1–4 μg/ cm2) in psoriatics (mainly in patients with type II psoriasis) than in healthy subjects (0.125–0.25 ug/cm2). Conclusions. The data indicate that increased beta-endorphin in psoriatic skin might affect both substance P-mediated neurogenic inflammation and transmission of sensory stimuli due to local antinociceptive effects of this opioid. The differences in the neurogenic response in type I and II psoriasis may be related to the degradation of substance P and beta-endorphin by neutral proteinases in the lesional skin.     

Unusual Inheritance of ABO Group in a Family with Weak B Antigens

The authors present the results of serological investigations of a family in which A₂B individuals have an atypical B antigen and anti-B antibodies in their serum. The B antigen is weaker than normal, but is easily detectable in routine blood grouping. The group is inheritable, and in two generations the A₂B individuals have a group O parent.

Résumé

Les auteurs présentent les résultats de recherches sérologiques chez une famille où des individus A₂B ont un antigène B atypique et des anticorps anti-B dans leur sérum. L'antigène B est plus faible que la normale, mais il est aisément mis en évidence lors de déterminations habituelles de groupes sanguins. Le groupe est héréditaire et, dans deux générations, les individus A₂B ont un des parents de groupe O.

Zusammenfassung

Die Autoren berichten über die Ergebnisse serologischer Untersuchungen in einer Familie, in welcher die A₂B-Individuen ein atypisches B-Antigen sowie Anti-B-Antikürper aufweisen. Das B-Antigen ist nur schwach ausgeprägt, jedoch bei Routine-Blutgruppenbestimmungen ohne Schwierigkeit nachweisbar. Die B-Ano-malie ist vererbt. Außerdem haben in zwei Generationen die A₂B-Individuen einen Elternteil mit der Blutgruppe O.     

IN VITRO ACTIVITY OF LYMPHOCYTES FROM CHILDREN WITH PRENATAL CYTOMEGALOVIRUS INFECTION

In vitro response of lymphocytes to phytohaemagglutinin (PHA) was normal or above normal in 9 children with prenatal cytomegalovirus (CMV) infection, and in 2 infants with early postnatal CMV infection. Increased activity of unstimulated lymphocytes was found in some infants with prenatal CMV, and in both infants with postnatal CMV. However, lymphocytes of some control infants also showed this phenomenon, which was common in the first 2 months of life, and was not found after 6 months of age.     

Developmental Toxicity of Acrolein in New Zealand White Rabbits

Pregnant New Zealand white rabbits (20 per group) were treatedvia stomach tube with 0.0, 0.1, 0.75, or 2.0 mg/kg/day fromDays 7 through 19 of presumed gestation and subjected to cesareansectioning on Day 29. Throughout the period of treatment, clinicalobservations, feed consumption, and body weights were recorded.At the termination of the study, reproductive and fetal parameterswere measured. Three does died during the study, and transienteffects on body weight gains and feed consumption were noted,with a subsequent rebound effect reflected in both fetal andmaternal weights in the high-dose group (2 mg/kg/day). Resorptionswere elevated in the high-dose group, but the effect was notstatistically significant. Fetal malformations were distributedevenly among groups, and incidences were consistent with historicalcontrol data on the same strain and at the same laboratory.Higher dosage levels (range-finding study, 4.0 and 6.0 mg/kg/day)produced high incidences of maternal mortality, spontaneousabortion, resorptions, clinical signs, gastric ulceration, and/orsloughing of the gastric mucosa. Acrolein was not found to bea developmental toxicant or teratogen at doses not toxic tothe does under the conditions employed in this study.     

Proarrhythmic Response to Antiarrhythmic Drug as a Risk Factor for Sudden Cardiac Death in Patients with Ischemic Heart Disease

The prognostic significance of arrhythmogenicc response to an antiarrhythmic drug was studied. In 782 palients with ischemic heart disease (IHD) and frequent and/or complex ventricular premature boats (VPBs), 1,041 drug tests guided by 24-hour Holter monitoring were conducted. The following drugs were assessed: beta blockers, disopyramide, mexiletine, amiodarone. Proarrhythmia was defined as: (1) > 4-fold increase in VPBs, (2) > 10-fold increase in repetitive forms, or (3) new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). During a follow-up of 1–49 months fmean 22) patients were treated with anfiarrhythmic drugs found to be safe in control Holter monitoring, Proarrhythmic effects were observed in 8.4% of patients. No drug was completely free of this type of reaction. In long-term observation, cardiac death and sudden death occurred in 5.3 and 32 patients, respectively. With actuarial analysis (Kaplan-Meier method, log-rank test) there was a significant difference in cardiac death (P < 0.01) and sudden death rate (P < 0.05) of proarrhythmia (+) compared with proarrhythmia (-) patients at 1 year (11% vs 4%, 7% vs 3%) and 3 years (24% vs 11%, 16% vs 7%). Proarrhythmic response was an independent risk factor apart from myocardial infarction, VT/VF, ejection fraction < 40% and QT_c > 440 msec. Arrhythmogenic response to antiarrhythmic drugs seems to be en additional predictor of sudden death in IHD.