Altered tubulin and neurofilament expression and impaired axonal growth in diabetic nerve regeneration

Cytoskeletal protein expression in sensory neurons and sciatic nerve axonal growth were examined in type 1 diabetic BB/Wor rats after sciatic nerve crush injury. Diabetic male rats were subjected to sciatic nerve crush at 6 wk of diabetes. L4 and L5 dorsal root ganglia (DRG) mRNA expression of low and medium molecular weight neurofilaments (NF-L, NF-M), betaII- and betaIII-tubulin as well as protein expression of NF-L, NF-M, and beta-tubulin were examined at various time points following crush injury and compared with age- and sex-matched non-diabetic BB/Wor rats. Steady state mRNA expression of NF-L, NF-M, betaII- and betaIII-tubulin were decreased in diabetic DRG. NF-L and NF-M proteins were also decreased in DRG of uncrushed diabetic animals. After crush injury, betaII- and betaIII-tubulin mRNA were upregulated in control animals at day 2 and day 6, respectively, and beta-tubulin protein showed similarly increased expression after crush injury, while such upregulations did not occur in diabetic animals. Conversely, mRNA and protein expressions of NF-L, NF-M were downregulated to a lesser extent in diabetic animals compared to control rats. These changes were associated with impaired axonal elongation and caliber growth of regenerating fibers in diabetic rats. We propose that upregulation of tubulin has a negative feedback on NF expression in response to nerve injury, as seen in control rats. The absence of this upregulation in diabetic animals may impair its regulatory effect on NF expression and contribute to perturbed nerve regeneration seen in diabetic nerve.     

C-peptide prevents hippocampal apoptosis in type 1 diabetes

To explore mechanisms underlying central nervous system (CNS) complications in diabetes, we examined hippocampal neuronal apoptosis and loss, and the effect of C-peptide replacement in type 1 diabetic BB/W rats. Apoptosis was demonstrated after 8 months of diabetes, by DNA fragmentation, increased number of apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied by reduced neuronal density in the hippocampus. No apoptotic activity was detected and neuronal density was unchanged in 2-month diabetic hippocampus, whereas insulin-like growth factor (IGF) activities were impaired. In type 1 diabetic BB/W rats replaced with C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were shown and DNA laddering was not evident in hippocampus at either 2 or 8 months. C-peptide administration prevented the preceding perturbation of IGF expression and reduced the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes causes a duration-dependent programmed cell death of the hippocampus, which is partially prevented by C-peptide.     

The effect of experimental Bothrops jararaca envenomation on pregnant mice.

The injury caused by the intramuscular injection of a single dose of Bothrops jararaca venom (0.24 mg/kg body weight) to mice on day 8 of pregnancy and examined on day 9 was investigated. Macroscopic and histological examination showed that the bothropic venom caused an increase in the incidence of fetal resorptions. Histologically, a characteristic involution of mature decidua was noticed in saline-treated mice; however, necrotic trophoblast giant cells and decidual cells were also present in this region of mice treated with B. jararaca venom, mainly close to the embryo. Hemorrhagic areas were also observed at maternal-fetal interface, which contained maternal erythrocytes and polymorphonuclears. Plasma fibrinogen levels were lower in envenomed group (p < or = 0.0001), but prothrombin time and activated partial thromboplastin time remained unaltered. Total and differential white blood cell counts were not statistically different between groups. Thus, B. jararaca venom causes injuries not only to the fetus, but also to decidual tissue and blood coagulation of pregnant mice. It is not clear, nonetheless, whether disturbances during the development of pregnancy are due to a direct effect of venom on uterus/fetus or to homeostatic changes in dams, such as clotting disturbances, or to both of them.     

The effectiveness of cost-effectiveness analysis in containing costs

OBEJCTIVE: Although cost-effectiveness analyses (CEAs) have been advocated as a tool to critically appraise the value of health expenditures, it has been widely hoped that they might also help contain health care costs. To determine how often they discourage additional expenditures, we reviewed the conclusions of recently published CEAs. DATA SOURCES: A search of the Abridged Index Medicus (a subset of MEDLINE designed to afford rapid access to the literature of “immediate interest” to the practicing physician) between 1990 and 1996. STUDY SELECTION: We only included articles that reported an explicit cost-effectiveness (CE) ratio (a cost for some given health effect) in the abstract. DATA ABSTRACTION: From each abstract, we collected the value for the incremental CE ratio and the measure of health effect (life-years, quality-adjusted life-years [QALYs], other). We then categorized the authors’ conclusion into one of three categories: supports strategy requiring additional expenditure, no firm conclusion, and supports low-cost alternative. Finally, we obtained the article and collected information on funding source. DATA SYNTHESIS: Among the 109 eligible articles, the authors’ conclusion supported strategies requiring additional expenditure in 58 (53%) and supported the low-cost alternative in 28 (26%). We then focused on the 65 articles reporting either life-years or QALYs. Cost-effectiveness ratios ranged from $400 to $166,000 (per life-year or QALY) in the 39 articles (60%) in which authors supported additional expenditure, and ranged from $61,500 to $11,600,000 in the 13 articles (20%) in which authors supported the low-cost alternative. Despite identifying similar CE ratios, authors arrived at different conclusions in the overlapping range ($61,500 to $166,000). Of the 10 articles acknowledging industry funding, 9 supported a strategy requiring additional expenditure (p=.01 as compared with those without such funding). CONCLUSIONS: Authors of CEAs are more likely to support strategies requiring additional expenditure than the low-cost alternative. There is no obvious consensus about how small the CE ratio should be to warrant additional expenditure. Finally, concerns about funding source seem to be warranted.     

Peripheral neuropathy in mutant diabetic mouse [C57BL/Ks (db/db)]

Summary A new animal model for the study of diabetic neuropathy is presented. The homozygote (db/db) of the mouse strain C57BL/Ks shows severe diabetes with longstanding hyperglycemia. Electrophysiological studies showed severely decreased motor nerve conduction velocity. Morphometric examination of sensory and motor nerves at different levels revealed absence of large myelinated fibers, with morphological features indicative of axonal atrophy.Supported by Grant No. MA-5857 from the Medical Research Council of Canada     

Post-traumatic acute appendicitis in hernia's sac

The paper presents two unusual pathological aspects of a hernia and an appendicitis. It is about a massive old inguinal hernia, with strangulation and an intra-saccular congestive acute appendicitis that occurred after a traumatic injury of the region. The presumptive diagnosis through a dynamic monitoring of the patient, clinical and biological analysis has made possible a favorable solution of the case.     

Compartment syndrome: an unusual course for a rare disease

We report a case of compartment syndrome of the left upper limb following hemorrhage due to Crimean-Congo hemorrhagic fever in a 45-year-old man. As far as we know, there is not such a report in the literature. We discuss clinical manifestations, electrophysiologic findings, differential diagnosis, and management of the patient. A high degree of awareness for an early diagnosis may participate to improve the poor prognosis.     

Gliosarcoma with cranial penetration and extension to the maxillary sinus

A 70 year old woman underwent an anterior rightsided temporal lobectomy for a mixed glioblastoma-fibrosarcoma. Six months later, she presented with rightsided zygomatic and maxillary swellings, associated with rightsided ptosis, chemosis, and nerve palsies of the III, IV, VI, and VII cranial nerves. A computerized scan (CT) of the head revealed tumor erosion of the skull base of the right middle fossa with extension into the maxillary sinus. This was confirmed at surgery. Pathologic examination revealed a predominantly small cell anaplastic glioblastoma associated with sarcoma elements, similar to the original intracranial tumor. This case documents a rare and atypical behavior of malignant glial tumors.