Escape reactions and variation in some genetic parameters in larva from the malaria mosquito Anopheles messeae

S-Methyl N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO) and sulfone (DETC-MeSO2) both inhibit rat liver low Km aldehyde dehydrogenase (ALDH2) in vitro and in vivo (Nagendra et al., Biochem Pharmacol 47: 1465-1467, 1994). DETC-MeSO has been shown to be a metabolite of disulfiram, but DETC-MeSO2 has not. Studies were carried out to further investigate the inhibition of ALDH2 by DETC-MeSO and DETC-MeSO2. In an in vitro system containing hydrogen peroxide and horseradish peroxidase, the rate of DETC-MeSO oxidation corresponded to the rate of DETC-MeSO2 formation. Carbamoylation of GSH by both DETC-MeSO and DETC-MeSO2 was observed in a rat liver S9 fraction. Carbamoylation of GSH was not observed in the presence of N-methylmaleimide. In in vitro studies, DETC-MeSO and DETC-MeSO2 were equipotent ALDH2 inhibitors when solubilized mitochondria were used, but DETC-MeSO was approximately four times more potent than DETC-MeSO2 in intact mitochondria. In studies with rats, the dose (i.p. or oral) required to inhibit 50% ALDH2 (ED50) was 3.5 mg/kg for DETC-MeSO and approximately 35 mg/kg for DETC-MeSO2, approximately a 10-fold difference. Furthermore, maximum ALDH2 inhibition occurred 1 hr after DET(-MeSO administration, whereas maximal ALDH2 inhibition occurred 8 hr after DETC-MeSO2 dosing. DETC-MeSO is, therefore, not only a more potent ALDH2 inhibitor than DETC-MeSO2 in vivo, but also in vitro when intact mitochondria are utilized. The in vitro results thus support the in vivo findings. Since oxidation of DETC-MeSO can occur both enzymatically and non-enzymatically, it is possible that DETC-MeSO2 is formed in vivo. DETC-MeSO2, however, is not as effective as DETC-MeSO in inhibiting ALDH2, probably because it has difficulty penetrating the mitochondrial membrane. Thus, even if DETC-MeSO2 is formed in vivo from DETC-MeSO, it is the metabolite DETC-MeSO that is most likely responsible for the inhibition of ALDH2 after disulfiram administration.     

Health counseling in adolescent preventive visits: effectiveness, current practices, and quality measurement

Most morbidity and mortality among adolescents results from their participation in health-compromising behaviors. Recent guidelines for clinical adolescent preventive services recommend that primary care clinicians routinely screen for and counsel adolescents about these behaviors, identify and address related social, psychological, and biologic factors. Office-based counseling can influence adult health behaviors, but little is known about the effectiveness of office-based counseling for adolescents. In this review we: (a) evaluate available information about the effectiveness of office-based health counseling to improve outcomes; (b) report what is known about the health counseling adolescents receive from primary care clinicians; and (c) critically review different approaches that have been, or might be, used to measure the content and quality of health counseling provided during adolescent medical visits. With the emphasis on accountability in the current health care environment, evidence supporting the effectiveness of counseling is needed to justify investment in this aspect of clinical adolescent preventive services. Challenges to studying the effectiveness of health counseling include the lack of well-defined theory-based models for adolescent office-based counseling, the complexity of measuring counseling quality, and the many factors that influence adolescent outcomes. Reliable and valid measures of counseling quality are needed both to study and to ensure the quality of counseling received by adolescents. No single measure can be expected to fully capture counseling quality, although patient self-report deserves further development.     

Video-thoracoscopic surgery

The experience in application of 24 videothoracoscopical operations in diseases and traumatic injuries of the organs of thoracic cavity (15-diagnostic and 9-curative ones) is reviewed. Histological verification of the diagnosis after the operative procedures was obtained in all 15 patients. The technique of TV thoracoscopic operations is outlined. Postoperation period in patients ran well, there were no substantial disturbances in function of external breathing, motor activity has restored on the second day after the operation.     

Confirmed abuse cases in public residential facilities for persons with mental retardation: a multi-state study

Our experience with 10 patients who suffered midshaft fractures of the femur and injuries to their ipsilateral hips has resulted in a treatment protocol that we believe can avoid unnecessary complications. The surgical protocol is a three-stage procedure based on (1) intramedullary nailing of the femur with interlocking for preserving the anatomic length and rotation of the femur; (2) treatment of the hip joint injury by means of open reduction and internal fixation of the acetabular fracture and/or reduction and fixation of the fractured femoral neck; and (3) repair of the extensor mechanism. Eight patients received this treatment and had fast recoveries. Union of the femoral fracture and full range of motion of the knee joint were observed within 3 months. In contrast, two patients who had received different surgical treatment had incomplete functional recoveries. This study offers a treatment protocol for ipsilateral disruption of the extensor mechanism, hip joint injury, and midshaft fracture of the femur in the multiply injured patient that can achieve full recovery with no complications. This relatively rare combination of injuries is definitely worthy of special attention.     

Expression of the human dystrophin gene in mdx mouse skeletal muscles after ballistic transfection

OBJECTIVE: This study aimed to determine the prevalence of sensorineural hearing loss (SNHL) in 2-5-year-old survivors with neonatal respiratory failure due to congenital diaphragmatic hernia (CDH) with or without the need for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: The study design was a prospective, multicenter, longitudinal outcome study of consecutively surviving neonates admitted to a single tertiary intensive care unit. SETTING: The study was conducted at four audiologic departments affiliated with tertiary-level intensive care follow-up programs. PATIENTS: Thirty-seven surviving children receiving neonatal intensive care from February 1989 through January 1995 for neonatal respiratory failure due to CDH were studied. Excluded were 15 children with early death and I child lost to follow-up. INTERVENTION: The initial treatment depended on the severity of neonatal respiratory failure: ECMO-treated (n=31, 20 survivors) (death before ECMO initiation, 2) and non-ECMO treated (n=20, 17 survivors, another survivor lost to follow-up). MAIN OUTCOME MEASURE: Early childhood audiologic test results were measured. RESULTS: Sensorineural hearing loss was found in almost 60% of subjects: ECMO-treated, 12 (60%) of 20; non-ECMO-treated, 10 (59%) of 17. Of the 22 children with SNHL, 16 had mild- to-moderate low-frequency sloping to moderate-to-severe high-frequency loss. Of the remaining, six had severe-to-profound loss at 500 Hz and above. Seventeen children had normal responses to sound as newborns or in infancy. Five children were not tested. Documented progression was found in nine children. Twenty children currently are using amplification, and 2 have had cochlear implantation. CONCLUSIONS: Of children with CDH in this area presenting early with severe neonatal respiratory failure, SNHL developed in 60% by 2-5 years of life. Ongoing monitoring of the hearing status of children with CDH is imperative.     

Relationship between action potential, contraction-relaxation pattern, and intracellular Ca2+ transient in cardiomyocytes of dogs with chronic heart failure

Abnormalities of contractile function have been identified in cardiomyocytes isolated from failed human hearts and from hearts of animals with experimentally induced heart failure (HF). The mechanism(s) responsible for these functional abnormalities are not fully understood. In the present study, we examined the relationship between action potential duration, pattern of contraction and relaxation, and associated intracellular Ca2+ transients in single cardiomyocytes isolated from the left ventricle (LV) of dogs (n = 7) with HF produced by multiple sequential intracoronary microembolizations. Comparisons were made with LV cardiomyocytes isolated from normal dogs. Action potentials were measured in isolated LV cardiomyocytes by perforated patch clamp, Ca2+ transients by fluo 3 probe fluorescence, and cardiomyocyte contraction and relaxation by edge movement detector. HF cardiomyocytes exhibited an abnormal pattern of contraction and relaxation characterized by an attenuated initial twitch (spike) followed by a sustained contracture ('dome') of 1 to 8 s in duration and subsequent delayed relaxation. This pattern was more prominent at low stimulation rates (58% at 0.2 Hz, n = 211, 21% at 0.5 Hz, n = 185). Measurements of Ca2+ transients in HF cardiomyocytes at 0.2 Hz manifested a similar spike and dome configuration. The dome phase of both the contraction/relaxation pattern and Ca2+ transients seen in HF cardiomyocytes coincided with a sustained plateau of the action potential. Shortening of the action potential duration by administration of saxitoxin (100 nM) or lidocaine (30 microM) reduced the duration of the dome phase of both the contraction/relaxation profile as well as that of the Ca2+ transient profile. An increase of stimulation rate up to 1 Hz caused shortening of the action potential and disappearance of the spike-dome profile in the majority of HF cardiomyocytes. In HF cardiomyocytes, the action potential and Ca2+ transient duration were not significantly different from those measured in normal cells. However, the contraction-relaxation cycle was significantly longer in HF cells (314 +/- 67 ms, n = 21, vs. 221 +/- 38 ms, n = 46, mean +/- SD), indicating impaired excitation-contraction uncoupling in HF cardiomyocytes. The results show that, in cardiomyocytes isolated from dogs with HF, contractile abnormalities and abnormalities of intracellular Ca2+ transients at low stimulation rates are characterized by a spike-dome configuration. This abnormal pattern appears to result from prolongation of the action potential.     

Restoration of peak vascular conductance after simulated microgravity by maximal exercise

Free radical-mediated injury is implicated in hypoxic-ischemic encephalopathy observed in neonates. We investigated in utero free radical production and injury following hypoxia-ischemia to premature fetal brain utilizing a rabbit model of acute placental insufficiency. Pregnant rabbits at 29 days gestation were randomized to uterine ischemia for 50 minutes (min) (hypoxia) or nonischemic controls. Fetal brains were obtained immediately after ischemia for oxidative and acute-injury markers or 24 hours (h) post-ischemia for histopathology. Nitrotyrosine formation, a marker of NO-derived species such as peroxynitrite, was observed only in hypoxic brains. Hypoxia resulted in a significant increase in nitrogen oxides, lipid peroxidation, and protein oxidation, with a concomitant decrease in total antioxidant capacity, compared with controls. Peroxynitrite addition to brain homogenate increased nitrogen oxides linearly (1:1), although protein carbonyls were unchanged. Concomitantly, in vitro cortical and hippocampal cell viability and ATP levels decreased, with an increase in brain edema in hypoxic brains. Fetuses delivered 24 h post-ischemia had increased hippocampal nuclear karyorrhexis on histology compared with controls. Antioxidant administration (ascorbic acid and Trolox) intraperitoneally ameliorated changes in cellular viability and brain edema. Acute fetal hypoxia-ischemia without reoxygenation results in increased nitrogen and oxygen free radical production that may cause brain injury. The merits of the described model are discussed.     

The triggering signal dictates the effect of docosahexaenoic acid on lymphocyte function in vitro

Three of the proteins protecting cells from autologous lysis by complement are: membrane cofactor protein (MCP; CD46), an inhibitor of the membrane attack complex formation (CD59), and decay accelerating factor (DAF; CD55). We have investigated the expression of these proteins in breast and colorectal carcinoma by immunohistochemistry and immunoblotting of breast tissue for CD46. CD46 was consistently and strongly expressed in the epithelial compartment in 26/28 ductal carcinomas of the breast, 9/9 fibroadenomas, and 9/11 cases of control non-neoplastic breast tissue. CD59 showed a similar degree of expression in the fibroadenomas (9/9), but was less strongly expressed in carcinomatous (22/28) and control (5/11) tissues. In marked contrast, no CD55 expression was detected in tissue from 15 ductal carcinomas. Immunoblotting of breast tissue for CD46 showed the same size of the molecule as for lymphocytes. It had however considerably stronger expression in tumour tissue than in non-neoplastic tissue. CD46 and CD59 were either lacking or only weakly expressed in the epithelial component of control colorectal mucosa: 2/15 and 5/15, respectively. In contrast, tissue samples from colorectal adenocarcinomas showed clear staining for both CD59 (10/18) and, more markedly, CD46 (15/18). There was no association between the pattern or intensity of CD46 and CD59 expression and tumour differentiation. As the complement regulatory proteins CD46 and CD59 are also strongly expressed by trophoblast at the feto-maternal tissue interface, these results support the concept that similar mechanisms are employed both by the genetically dissimilar fetus and certain tumours to evade immune attack by their host.     

Outcomes of balloon coronary angioplasty of bifurcation stenoses in patients with ischemic heart disease

Specialists of the Research Institute of Urology have practiced combination of transurethral resection (TUR) with electrovaporization in endoscopic treatment of bladder cancer (BC) since 1995. A total of 46 patients with transient cell BC (29 males and 17 females aged 49-87) stage Ta-T1 (32 patients) and T2-T3b (14 patients) underwent TUR or electrovaporization (if morphologically verified) of the exophytic part of the tumor. In addition, electrovaporization of the base of the tumor was made. Main indications for such treatment were standard indications for TUR in contraindications for more radical treatment. 6-24-month follow-up was possible in 23(71.9%) patients with superficial BC (group 1) and in 9(64.2%) patients with invasive BC (group 2). Endoscopically, the recurrence was detected in 3(13%) and 5(55.5%) patients of group 1 and 2, respectively. They were reoperated on with electrovaporization. It is inferred that TUR-vaporization of the bladder is an effective endoscopic treatment of superficial BC. Electrovaporization is a good palliative treatment in patients with invasive BC when radical surgery is impossible. It inhibits the progression of the disease, prevents hemorrhages due to the tumor destruction, reduces intraoperative blood loss, improves endoscopic visualization. It may also increase the operation ablasticity.     

The past, present and future of cell pathology problems

Three stages of development in cellular pathology are analyzed. Evaluation of important achievements in the past which permitted the advance to the present stage in cellular pathology is given. New methods in experimental pathology resulted in the appearance of a new direction--molecular morphology and molecular cell pathology. The basic features of this direction and new problems to be resolved are formulated.