Novel patterns of left ventricular mechanical activity during experimental cardiac arrest in pigs.

We conducted an experimental study to evaluate the presence of coordinated left ventricular mechanical myocardial activity (LVMA) in two types of experimentally induced cardiac arrest: ventricular fibrillation (VF) and pulseless electrical activity (PEA). Twenty anesthetized domestic pigs were randomized 1:1 either to induction of VF or PEA. They were left in nonresuscitated cardiac arrest until the cessation of LVMA and microcirculation. Surface ECG, presence of LVMA by transthoracic echocardiography and sublingual microcirculation were recorded. One minute after induction of cardiac arrest, LVMA was identified in all experimental animals. In the PEA group, rate of LVMA was of 106+/-12/min. In the VF group, we identified two patterns of LVMA. Six animals exhibited contractions of high frequency (VFhigh group), four of low frequency (VFlow group) (334+/-12 vs. 125+/-32/min, p<0.001). A time from cardiac arrest induction to asystole (19.2+/-7.2 vs. 7.3+/-2.2 vs. 8.3+/-5.5 min, p=0.003), cessation of LVMA (11.3+/-5.6 vs. 4.4+/-0.4 vs. 7.4+/-2.9 min, p=0.027) and cessation of microcirculation (25.3+/-12.6 vs. 13.4+/-2.4 vs. 23.2+/-8.7 min, p=0.050) was significantly longer in VFlow group than in VFhigh and PEA group, respectively. Thus, LVMA is present in both VF and PEA type of induced cardiac arrest and moreover, VF may exhibit various patterns of LVMA.

The impact of immunosuppression on erythema migrans. A retrospective study of clinical presentation, response to treatment and production of Borrelia antibodies in 33 patients.

BACKGROUND: Little is known about the potential influence of immunosuppression on erythema migrans, the hallmark of early Lyme borreliosis. METHODS: We performed a retrospective study to assess the impact of immunosuppression on erythema migrans in 33 patients with a malignant or autoimmune disease, chronic infection, or immunosuppressive therapy for organ transplantation. Only patients with active disease status and/or current immunosuppressive therapy were included. Pre-treatment clinical parameters, such as presentation of the skin lesion and presence of extracutaneous signs and symptoms, the disease course during a median follow-up of 9 months after therapy and serum anti-Borrelia burgdorferi antibodies before therapy and by the end of follow-up in the 33 immunosuppressed patients were statistically compared with 75 otherwise healthy patients with erythema migrans. The 75 control patients were matched for sex, age and antibiotic therapy. RESULTS: With the exception of the site of erythema migrans lesions, which were found more often on the trunk than on the legs in the immunosuppressed patients (vice versa in immunocompetent patients), we found no significant differences for all investigated parameters between the two groups. CONCLUSIONS: It appears that immunosuppression does not influence clinical presentation, response to therapy, or production of anti-B. burgdorferi antibodies of patients with erythema migrans. It is thus not necessary to treat immunosuppressed patients with erythema migrans differently from immunocompetent patients.

Activins and activin receptors in cell growth.

Activin and inhibin, members of transforming growth factor-beta (TGFbeta) superfamily, have diverse and widespread effects within living organisms at many stages during growth and development. From the initial isolation of these growth factors based on their effects of FSH secretion, the study of these factors, as well as of the activin-binding protein follistatin, has progressed from the localization of the expression of the inhibin alpha subunit, activin betaA and betaB subunits, and activin receptors in the tissues of various organisms to the examination of activin and inhibin as autocrine and paracrine agents in cell proliferation and differentiation. The inhibitory effects on cell growth and differentiation that have been observed upon treatment of cells with activin suggest that further understanding of the bioactivity of this molecule and its characterization on a molecular level may aid in a more complete understanding of cell growth and differentiation. This minireview discusses the roles of activin, inhibin, and follistatin in the arenas of cell proliferation, differentiation, and embryogenesis, as well as the roles of these molecules in cancerous cells.

Expression of activin and activin receptors in human prostatic-carcinoma cell-line du145.

The purpose of this study was to determine whether DU145, a human prostate cancer cell line: (a) transcribes mRNAs coding for beta A- and beta B-subunits of activin, a member of transforming growth factor beta (TGF beta) superfamily, and activin receptors I, II, and IIB; and (b) produces activin proteins. The expression and localization of the mRNAs were elucidated by the reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization techniques. The production of activin was determined by immunocytochemistry. We have observed that messenger RNAs encoding activin beta A-, beta B-subunits, and activin receptors I, II, and IIB, but not that of the alpha-subunit of inhibin, were expressed, and activin proteins, but not inhibin, were produced, by DU145 cells. Furthermore, the RT-PCR products were confirmed by DNA sequencing. It is concluded that activins and their receptors are expressed in DU145 and activins may have autocrine functions in DU145 cells.

Cardenolides in Digitalis lanata Cells Transformed with Ti-Plasmids.

Crown galls were induced by transformation of leaves, leaf discs, and shoots of the plant DIGITALIS LANATA with the AGROBACTERIUM TUMEFACIENS strains C58 pTi C58, B6S3 pTi B6S3, and A136 pTi A6NCtmr-338::Tn5. Integration of plasmid DNA in the genome of D. LANATA was demonstrated by hybridization experiments. The transformed cells synthesized opines and showed hormone-autotrophic growth. The crown galls formed on leaves of D. LANATA plants contained digitoxigenin derivatives (up to 0.8 muimol digitoxin equivalents g (-1) dry weight). Transformed cell lines derived from the crown galls built cardenolides IN VITRO (ca. 0.03 mumol digitoxin equivalents g (-1) dry weight). The rate of cardenolide biosynthesis IN VITRO did not decrease during a cultivation period of 12 months.

[EDLS (endogenous digitalis-like substance(s))--detection, chemistry, and physiologic function]. / EDLS [Endogenous digitalis-like substance(s)]--Nachweis, Chemie, physiologische Bedeutung.

Human beings and higher animals contain compounds which interact with the Na+/K+-ATPase of the heart muscle and other organs like the cardiac glycosides, and bind to cardiac glycoside-specific antibodies [endogenous digitalis-like substance(s), EDLS]. EDLS cause increased natriuresis. The level of EDLS of the blood is raised under physiological stress situations (e.g., pregnancy and delivery and at certain pathophysiological conditions (e.g., hypertony). The EDLS are low molecular compounds. As yet their chemical structure is unknown.

A study of interfering herpes simplex virus DNA preparations containing defective genomes of either class I or II and the identification of minimal requirements for interference.

Progeny DNA of herpes simplex virus type 1 (HSV-1) strain ANG from infections involving defective interfering virus particles (DI DNA) has been described to be of low infectivity in transfection assays due to the presence of viral genomes that interfere with plaque formation by infectious standard genomes. In this study it is shown that this observation applies both for DI DNA containing repetitive defective DNA of the class I type and for DI DNA containing class II-type defective DNA. Restriction endonucleases with recognition sites only in one class of repetitive defective DNA could be used to reduce selectively the interfering activity of DI DNA preparations containing the respective defective DNA in abundance. The results obtained directly implicate repetitive defective DNA as an interfering agent. Restriction endonucleases that create monomeric DNA fragments from class II HSV-1 ANG defective DNA did not abolish the interfering activity of DI DNA containing this type of defective DNA in high abundance, indicating that it is not simply the repetitive nature of defective DNA that is required for interference. Certain DNA fragments shorter than the repeat unit of repetitive defective DNA were still capable of causing interference even in the absence of cohesive single-stranded ends. The common location of cis recognition signals responsible for progeny DNA maturation and initiation of DNA replication on one DNA fragment, however, appeared to be a minimal requirement for interference by fragmented defective DNA.

Experience with low-dose insulin infusion in diabetic ketoacidosis and diabetic hyperosmolarity.

Forty patients with diabetic ketoacidosis and eight patients with the diabetic hyperosmolar state were treated with low-dose insulin infusion in four teaching hospitals in the Cleveland area. The clinical and biochemical responses observed support previous favorable reports on this treatment modality. Two elderly patients with the hyperosmolar syndrome died. The advantages of this form of treatment over intermittent insulin schedules are emphasized. Early potassium administration, unless otherwise contraindicated, is recommended. Rarely, increasing doses of insulin may be required if insulin resistance is encountered.

Impaired Leydig cell reserve and altered serum androgen binding in the aging male.

The hormonal profile of the aging male reveals an associated decrease in free testosterone and 5 alpha-dihydrotestosterone (DHT) levels and increased luteinizing hormone levels. Later events consist of a decrease in total testosterone, stable DHT, and increased follicle-stimulating hormone and estradiol levels. Although most available information supports the concept of impaired Leydig cell reserve, our study suggests some degree of hypothalamic-pituitary dysfunction. The signal for increased androgen binding with age is not clear. There is a great deal of individual variation in the time of onset of these events.