Inhibition of rat mammary carcinogenesis by monoterpenoids

We have previously demonstrated the cancer chemopreventive activities of the monocyclic unsaturated monoterpene d-limonene. In the present work we report data evaluating the chemopreventive effects of limonene and five other monoterpenes with various chemical structures using a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis model. The terpenes tested include: oxygenated [(-)-menthol] and non-oxygenated (d-limonene) monocyclic forms, oxygenated (1,8-cineole) and non-oxygenated [(+/-)-alpha-pinene] bicyclic forms and oxygenated [(+/-)-linalool] and non-oxygenated (beta-myrcene) acyclic forms. Dietary additions of each of the monocyclic terpenes, d-limonene or (-)-menthol resulted in a significant inhibition of mammary carcinogenesis. Furthermore, menthol was found to be a more potent chemopreventive agent than limonene during the DMBA initiation of rat mammary tumors. The acyclic and bicyclic terpenes had no significant chemopreventive activities at the dose levels used in these studies.     

Case report: The cobweb syndrome: first trimester sonographic diagnosis of multiple amniotic bands confirmed by fetoscopy and pathological examination

Amniotic band syndrome is a well described clinical entity presentingwith deformities of the limbs, thorax, craniofacial skeleton,soft tissues and umbilical cord, but it still lacks a precisedefinition and a coherent hypothesis for its pathogenesis. Wereport on a case of first trimester diagnosis of amniotic bandsyndrome by sonography and fetoscopy. This revealed multipleabnormalities including facial cleft, brain and limb deformities;the appearance of the amniotic cavity was that of a cobweb containingthe fetus. Postmortem examination and histopathological studiesconfirmed the diagnosis of amniotic band syndrome. These resultsmay enhance the knowledge of its natural course. In addition,based on histological and newly identified ultrastructural features,we present a hypothesis which could help to explain the aetiopathogenesisof the amniotic band syndrome.     

Inhibition of mast cell sensitization in vitro by a human immunoglobulin epsilon-chain fragment synthesized in Escherichia coli

An immunoglobulin epsilon-chain fragment was synthesized in E. coli by cloning and expression of the gene coding for the second, third and fourth constant domains of the human IgE heavy chain. The bacterial CH2-4 polypeptide product was assembled by oxidation into a covalently linked dimeric epsilon-chain molecule presumably analogous to the Fc region of native IgE. This bacterial Fc epsilon preparation, within the concentration range 0.01-10 micrograms/ml, inhibited sensitization of human lung mast cells, determined as histamine released upon challenge with specific antigen. Monomer CH2-4 epsilon-chain polypeptide, prepared by reduction and alkylation of the active bacterial Fc epsilon fragment, was inactive as an inhibitor of sensitization. The molar potency of the active bacterial Fc epsilon product was approximately one fourth of that of native IgE. Since the bacterial Fc epsilon is nonglycosylated, carbohydrate does not make an essential contribution to the Fc receptor binding activity of IgE. These results show that a functionally active immunoglobulin molecule can be synthesized by gene cloning and expression in E. coli.     

Mirizzi syndrome simulating a tumor by ERC

Summary ERC was initially performed on a patient with right upper quadrant pain and jaundice. The filling defect in the CHD was felt to be a tumor. A correct preoperative diagnosis of Mirizzi's syndrome was made by CT.     

Contraception and the cervix

In the human and subhuman primates the uterine cervix plays an important role in the reproductive process by its permissive and inhibitory action on sperm migration from the vaginal pool into the cervical canal, the uterine cavity and the fallopian tube, the site of gamete unification and fertilization. This is accomplished through physico-chemical (amount, clarity, viscosity, pH, electrolyte composition, etc.) alteration of the cervical mucus in response to the circulating sex steroids. In an ovulatory cycle, shortly prior to and at the time of ovulation the cervical mucus becomes most receptive to the spermatozoa whereas at other times, specifically following ovulation, it becomes hostile to the spermatozoa and virtually impenetrable. This unique property of the cervical mucus may, in addition to the presently available techniques (diaphragm, cervical cap and intracervical devices), allow identification of such potential contraceptive modalities as: pH modifier - changing the pH of the cervical mucus from alkaline to acid around the time of ovulation; Electrolyte modifier - changing electrolyte composition of the cervical mucus to produce a mesh impenetrable to spermatozoa. Finally, development of a temporary localized tissue-fixed immune antibody to spermatozoa in the cervical mucus is within the realm of reality and deserves the necessary attention.     

Further studies on the pharmacokinetics of perhexiline maleate in humans

We have performed single-dose pharmacokinetic studies on perhexiline in eight young volunteers, each given 300 mg of Pexid orally, using an h.p.l.c. method for the separation and quantification of the drug and its monohydroxy metabolites in plasma and urine. The plasma concentration of the cis-monohydroxyperhexiline (peak of 473 +/- 43 ng/ml at 7.5 +/- 2.0 h) was always higher than for unchanged perhexiline (peak of 112 +/- 20 ng/ml at 6.5 +/- 2.0 h) whereas the concentration of the transmetabolite was either low or undetectable in plasma. These findings indicate the occurrence of stereospecific pre-systemic metabolism of perhexiline which reduces the bioavailability of the parent drug. The plasma elimination half-life of perhexiline was 12.4 +/- 6.1 h (range 7-23 h) while that for cis-monohydroxyperhexiline was 19.9 +/- 7.7 h (range 10-29 h). Not more than 0.3% of unchanged perhexiline was excreted in the urine over five days in eight subjects. Between 3 and 23% of the orally administered drug was excreted as the cis- or trans-monohydroxy metabolites, the ratio of trans to cis metabolites being 0.52 +/- 0.20.     

Toward constructing an endophenotype strategy for bipolar disorders.

Research aimed at elucidating the underlying neurobiology and genetics of bipolar disorder, and factors associated with treatment response, have been limited by a heterogeneous clinical phenotype and lack of knowledge about its underlying diathesis. We used a survey of clinical, epidemiological, neurobiological, and genetic studies to select and evaluate candidate endophenotypes for bipolar disorder. Numerous findings regarding brain function, brain structure, and response to pharmacological challenge in bipolar patients and their relatives deserve further investigation. Candidate brain function endophenotypes include attention deficits, deficits in verbal learning and memory, cognitive deficits after tryptophan depletion, circadian rhythm instability, and dysmodulation of motivation and reward. We selected reduced anterior cingulate volume and early-onset white matter abnormalities as candidate brain structure endophenotypes. Symptom provocation endophenotypes might be based on bipolar patients' sensitivity to sleep deprivation, psychostimulants, and cholinergic drugs. Phenotypic heterogeneity is a major impediment to the elucidation of the neurobiology and genetics of bipolar disorder. We present a strategy constructed to improve the phenotypic definition of bipolar disorder by elucidating candidate endophenotypes. Studies to evaluate candidate endophenotypes with respect to specificity, heritability, temporal stability, and prevalence in unaffected relatives are encouraged.     

Potentially fatal cardiac dysrhythmia and hyperkalemic periodic paralysis

An 11-year-old boy was evaluated for mild periodic muscular weakness exacerbated on separate occasions by disopyramide phosphate and procainamide. He and his mother both had bidirectional ventricular tachydysrhythmia (BVT), short stature, microcephaly, and clinodactyly. The mother, but not the child, had lingual myotonia. The two antiarrhythmic drugs worsened the muscular weakness without benefiting the cardiac dysrhythmia. Potassium loading produced skeletal muscle weakness and transient conversion of the BVT to normal sinus rhythm. Hypokalemia aggravated the BVT without causing weakness. Acetazolamide had no effect. The patient suffered a nonfatal cardiac arrest after several days of increased carbohydrate intake. Imipramine controlled the dysrhythmia without inducing weakness. Periodic paralysis should be considered as the diagnosis in children with BVT, a potentially fatal condition.