Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. Plasma Cannabinoid and Blood Carboxyhemoglobin Concentrations and Clinical Chemistry Parameters

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. PlasmaCannabinoid and Blood Carbxyhemoglobin Concentrations and ClinicalChemistry Parameters SLIKKER, W., JR., PAULE, M. G., ALI, S.F., SCALLET, A. C., AND BAILEY, J. R (1991). Fundam. Appl Toxicol17, 321–334. This report is the first in a series abouta large multidisciplinary study designed to determine whetherchronic marijuana (MJ) smoke exposure results in residual behavioraland/or neuropathological alterations in the rhesus monkey. Priorto the initiation of a year of chronic MJ smoke exposure, 64periadolescent male rhesus monkeys were trained for 1 year toperform five operant behavioral tasks and then divided, accordingto their performance in these tasks, into four exposure groups(n=15–16/group): (1) a high dose (HI) group, exposed 7days/week to the smoke of one standard MJ cigarette; (2) a lowd m (LO) group, exposed on weekend days only to the smoke ofa standard MJ cigarate; (3) an extracted MJ cigarette (EX) group,exposed 7 days/week to the smoke of one ethanol-extracted MJcigarette; and (4) a sham group (SH), exposed 7 days/week tosham exposure conditions. Daily exposures for 1 year were accomplishedusing a mask that covered the subjects' nose and mouth. Averagebody weights (initially 3.7?0.5 kg, mean?SD) and rates of weightgain (approximately 0.1 kg/month) were the same for all groupsthroughout the entire experiment. During the first week of expsure,plasma concentrations of -9-tetrahydrocannabinol and 11-nor-9-carboxy-THCin the HI group were 59?7 (mean?SE) and 5.5?1.5 ng/ml, respectively,45 min after MJ smoke administration and did not change significantlyat similar times after exposure throughout the remainder ofthe year. Whole blood carboxyhemoglobin levels increased toapproximately 13% 1 min after expsure to smoke in either theMJ or the EX groups. Comparison of blood chemistry and hematologyvalues before, during, and after exposure indicated no differencesfor most parameters. During exposure, lymphocytes, alkalinephosphatase and -glutamyl transferase were depressed in theHI group compared to in the SH group. During exposure, aspartateaminotransferase was elevatd for both the HI and EX groups,suggesting a general effect of smoke exposure. Because theseeffects were transient and remained within the range of reportednormal values, these data indicate that long-term, experimentalexperimental exposure to MJ smoke is feasible and does not compromisethe general health of the rhesus monkey.     

The Effects of Rate and Rhythm Control on Blood Pressure and Antihypertensive Drug Usage in Patients with Atrial Fibrillation and Hypertension Enrolled in the AFFIRM Trial

AF and HTN in the AFFIRM trial . Introduction: Atrial fibrillation (AF) has been shown to be associated with activation of the renin–angiotensin–aldosterone system, endothelial dysfunction, and increased sympathetic activity, all of which could lead to hypertension (HTN). While the effects of HTN on AF incidence and arrhythmogenesis have been reported, the long‐term effects of AF on blood pressure (BP) remain unknown. We hypothesized that a rate control strategy is associated with an increase in BP and/or antihypertensive drug therapy when compared with a rhythm control strategy in patients with a history of AF and HTN. Methods and Results: Using the intention to treat method, BP readings and the number of antihypertensive medication categories were analyzed over the first year of follow‐up in patients with AF and HTN enrolled in the AFFIRM trial. No clinically significant changes in BP occurred. Medication data were available in 2,876 patients. In the rate control group, 27.8% of patients required a net increase in the number of antihypertensive medications when compared to 18.3% in the rhythm control group (P < 0.001). Furthermore, 27.1% of patients in the rate control group had a net decrease in the number of antihypertensive medications when compared with 41.7% in the rhythm control group (P < 0.001). Conclusions: Our findings suggest that AF could be contributing to BP elevation in patients with a history of HTN and that a rhythm control strategy might result in a decrease in BP in these patients. This hypothesis however, requires future testing. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1094‐1098)     

Correlation of Spontaneous and Induced Premature Atrial Complexes Initiating Atrial Fibrillation in Humans: Electrophysiologic Parameters for Guiding Therapy

INTRODUCTION: The low frequency of spontaneous premature atrial contractions (PACs) may be an impediment to mapping and ablation of atrial fibrillation (AF). It has been shown that PACs following external or internal cardioversion of AF can initiate AF. If this method could reproducibly induce PACs from the same location as spontaneous PACs, it would be clinically significant. High-resolution noncontact mapping can map a single beat, should help identify the sites of spontaneously occurring PACs and PACs induced following cardioversion of spontaneous or induced AF, and could help correlate the trigger sites for AF induction. METHODS AND RESULTS: Twelve patients (8 men and 4 women; mean age 49+/-10 years) with spontaneous PACs were included in the study. In all patients, AF was induced and subsequently cardioverted to assess and map isolated PACs or PACs that induced AF. Using the EnSite 3000 noncontact mapping system, mapping was performed of spontaneously occurring isolated PACs and PACs that induced AF and PACs (both with and without AF) that occurred on at least two different occasions following cardioversion. The locations of the spontaneous and the induced PACs were similar; 97% of induced PACs came from the same locations as those of spontaneous PACs (P = 0.5). Radiofrequency lesions guided by this mapping technique were delivered at 14 pulmonary vein sites. Following a single ablation attempt during a mean follow-up of 19+/-4 weeks, 42% of the patients were in sinus rhythm and drug-free, whereas an additional 24% of patients could be maintained in sinus rhythm on drugs that had failed before. CONCLUSION: There is a high degree of correlation between spontaneous and induced PACs as the trigger sites for AF initiation. Cardioversion of spontaneous or induced AF could be used as an electrophysiologic parameter for guiding therapy.     

Metachronous testicular teratoma,testicular seminoma and papillary thyroid carcinoma occurring in a single individual: a report of two unrelated cases

SYED A.A., JONES N.A.G., BLISS R.D., ROBERTS J.T., MALLICK U.K., JOHNSON S.J., DOUGLAS S.F., PERROS P. & QUINTON R. (2010) European Journal of Cancer Care 19 , 701–702 Metachronous testicular teratoma, testicular seminoma and papillary thyroid carcinoma occurring in a single individual: a report of two unrelated cases We describe two unrelated men who both developed teratomas in one testis followed by seminomas in the contralateral testis followed by papillary thyroid carcinomas. Neither man had a family history of cancers. Although random occurrence is possible, genetic predisposition and/or environmental influence would seem a likely explanation for this previously unreported combination of tumours.     

Hormonal regulation of a rat seminiferous tubule factor which inhibits LH action on interstitial cells

The cytosol from rat testes or seminiferous tubules contains a factor that markedly reduces the responsiveness of interstitial cells to stimulation by LH. It was noted previously that the inhibitor cannot be found until 35 days of age, suggesting that gonadotrophic stimulation of the testes is of importance for its formation. In the present studies, treatment of intact 20-day-old rats with FSH or with a combination of FSH and LH caused a premature appearance of the inhibitory activity. LH alone had a weak effect. However, hypophysectomy at 20 or 35 days of age did not influence the inhibitor content of the testes. Moreover, when the Leydig cells of adult rats were destroyed selectively by treatment with ethylene dimethane sulphonate, inhibitor levels were unchanged. It is suggested that induction of the Leydig cell inhibitor is under the control of FSH. However, once induced, its regulation seems to be independent of the pituitary gland. In separate experiments, ligation of the efferent ducts of the testes in adult animals did not cause any accumulation of inhibitory activity in the ligated testes, nor could the inhibitor be traced in the caput epididymis. Thus, it does not seem to be secreted into the epididymis, but rather may act as a paracrine factor in the testis.     

Cyclic bisbibenzyls induce growth arrest and apoptosis of human prostate cancer PC3 cells

Aim:

To investigate the cytotoxic effects of four cyclic bisbibenzyls, Riccardin C (Ric), Pakyonol (Pak), Marchantin M (Mar), and Plagiochin E (Pla) against chemoresistant prostate cancer PC3 cells.

Methods:

Cell growth was assayed by MTT method, and apoptotic related protein Bcl-2 and Bax, poly(ADP-ribose) polymerase (PARP) were examined by Western blotting. Cell cycle and apoptosis of PC3 cells were evaluated with flow cytometry and morphologic examinations.

Results:

The four compounds inhibited proliferation and elicited cell death in a dose- and time-dependent manner with IC₅₀ values of 3.22 μmol/L for Ric, 7.98 μmol/L for Pak, 5.45 μmol/L for Mar, and 5.99 μmol/L for Pla, respectively. Furthermore, exposed to these chemicals caused a decrease in the antiapoptotic protein Bcl-2 and an increase in proapoptotic Bax expression. PARP cleavage and caspase-3 activity were also observed.

Conclusion:

The results suggest that cyclic bisbibenzyls could be used for the development of novel therapeutic chemicals against prostate cancer.     

Prevalence of a Brugada Pattern Electrocardiogram in an Urban Population in the United States

Objective: To determine the prevalence of a Brugada-type pattern on routine electrocardiogram (ECG) in an urban population served by a tertiary medical center in the United States.
Methods: The investigators reviewed the ECG database at the Montefiore Medical Center, a tertiary teaching center in the Bronx, New York, over a 10-year period. During this time, 653,006 ECG records in 162,590 patients were identified. The database was queried by applying standard diagnostic criteria in an attempt to identify records with apparent conduction delay and ST abnormality in leads V1–V3. Additional diagnostic criteria were then applied to identify records in an attempt to mimic Brugada-like changes. A cardiac electrophysiologist reviewed records meeting these criteria to confirm the presence of a Brugada-type pattern.
Results: In total, 16,067 patients (9.8%) were identified as having ECGs with right bundle branch block, incomplete right bundle branch block, or RSR' in leads V1 and V2. After applying additional diagnostic criteria evaluating ST segment shift, 456 patients were identified as having a pattern potentially consistent with a Brugada-type ECG. The presence of a Brugada-type pattern was confirmed by physician overread in 20 patients (0.012%).
Conclusion: The Brugada-type ECG pattern is infrequently seen in a large ethnically diverse urban US population. Further evaluation should be considered when this pattern is seen on routine ECG.