An Autopsy Case of Tracheal Agenesis with Broncho-esophageal Fistula

Abstract True incidence of this malformation is probably greater than that reported since the definitive diagnosis has been made at autopsy in most cases. Various hypotheses on the pathogenesis of tracheal agenesis have been proposed but they are still controversial.
In this report, we present a case of tracheal agenesis with a broncho-esophageal fistula and discuss the formal genesis.     

Modulation of infection-induced inflammation and locomotive deficit and longevity in senescence-accelerated mice-prone (SAMP8) model by the oligomerized polyphenol Oligonol.

Oligonol is produced from the oligomerization of polyphenols (typically proanthocyanidin from a variety of fruits such as lychees, grapes, apples, persimmons, etc.) and contains catechin-type monomers and oligomers of proanthocyanidins. The ability of Oligonol to affect infection-dependent eye inflammation, locomotion and longevity in senescence-accelerated prone mice (SAMP8) (a model of senescence acceleration and geriatric disorders with increased oxidative stress and neuronal deficit) was investigated. Oligonol (60mg/kg) significantly modulated the extent of inflammation scores in the eye of SAMP8 mice. Examination of the mice indicated infection with mouse hepatitis virus and pinworm (Syphacia obvelata) in both males and females and with the intestinal protozoa (trichomonad) in males. A comparison of the two groups (using log-rank test) and the difference in the mean life span between groups (using Student's t-test) indicated significant differences in survival (p=0.043) and the mean life span (p=0.033) in male SAMP8 mice. Oligonol increased the mean life span and this was statistically significant. In the open-field locomotive test, the 7-week-old SAMP8 mice crossed more than 40 partitioned lines in 1min. At 48-week-old control untreated male SAMP8 crossed 2 lines. The Oligonol-treated 48-week-old male SAMP8 mice crossed 17 lines however. The improved locomotive activity was statistically significant even after 36weeks in the Oligonol-treated male SAMP8 but this was not the case throughout the time course of the study in the Oligonol-treated female SAMP8. Thus Oligonol treatment to SAMP8 mice modulated the severity of infection-dependent inflammation, prolonged life-span and significantly improved locomotive activity indicating potential benefit to aging-associated diseases such as Alzheimer's or Parkinson's diseases. This presents potential for further research to define infection-dependent inflammation associated with degenerative conditions and the molecular mechanism of dietary antioxidant protection.     

Preferential inhibitions of hepatic P450IA2 expression and induction by lead nitrate in the rat

Male F344 rats were treated with lead nitrate and changes inthe expression and induction of P450IA subfamily enzymes anda placental form of glutathione-S-transferase (GST-P) in theliver were assessed by means of a bacterial mutation test, immunoblottingwith a monoclonal antibody reactive to P450IA1/IA2 and anti-GST-Psera and Northern blotting with P450IA2 cDNA as a probe. Treatmentof rats with lead nitrate (20, 50 or 100 µmol/kg bodywt) decreased P450IA2 mRNA and protein in the liver in the dose-dependentfashion and also decreased the microsomal activity for P450IA2-dependentmutagenization of aromatic amines. Pretreatment of rats withlead nitrate suppressed the inductions of both P450IA2 mRNAand protein by an inducer of P450IA subfamily enzymes in theliver. In addition, amount of the induced P450IA2 was decreasedalong with increase in that of the induced GST-P.     

Mechanisms underlying the enhanced elevation of IL-1beta and TNF-alpha mRNA levels following endotoxin challenge in rat alveolar macrophages cultured with low-Mg2+ medium.

We have previously shown that interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha mRNA levels in rat alveolar macrophages are increased in by endotoxin (lipopolysaccharide; LPS)- stimulation and further enhanced by culturing with low-Mg2+ medium. We have now investigated the mechanisms of underlying this enhancement by using some specific signal transduction inhibitors. The enhanced elevation of both mRNAs levels was suppressed by pretreatment with TMB-8 (which inhibits calcium release from the endoplasmic reticulum) or dexamethasone (which inhibits nuclear factor [NF]-kappaB and activator protein [AP]-1), but not with verapamil or nifedipine (which inhibits calcium channels). The enhancment of IL-1beta, but not TNF-alpha mRNA levels, was suppressed by pretreatment with W-7 (which inhibits calmodulin), whereas the enhancement of TNF-alpha mRNA levels was suppressed by pretreatment with U73122 (which inhibits phospholipase C). Curcumin (an inhibitor of AP-1), suppressed the increases in both mRNAs induced by low-Mg2+ medium alone, but had no suppressive effect on the levels of either mRNA after LPS-stimulation in low-Mg2+ medium. Pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB) prevented the elevation of TNF-alpha mRNA levels induced by low-Mg2+ medium without LPS-stimulation, but had no suppressive effect on IL-1beta mRNA levels. From these results, we conclude that the enhanced elevation of IL-1beta and TNF-alpha mRNA levels seen in LPS-stimulated alveolar macrophages in low-Mg2+ medium occurs partly via the same, and partly via different, signaling pathways.     

Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats.

Recent studies have revealed that the phosphatidylinositol 3-kinase (PI3-K) pathway is involved in apoptotic cell death after experimental cerebral ischemia. The serine-threonine kinase, Akt, functions in the PI3-K pathway and prevents apoptosis by phosphorylation at Ser473 after a variety of cell death stimuli. After phosphorylation, activated Akt inactivates other apoptogenic factors, including glycogen synthase kinase-3beta (GSK3beta), thereby inhibiting cell death. However, the role of Akt/GSK3beta signaling in the delayed death of hippocampal neurons in the CA1 subregion after transient global cerebral ischemia (tGCI) has not been clarified. Transient global cerebral ischemia for 5 mins was induced by bilateral common carotid artery occlusion combined with hypotension. Western blot analysis showed a significant increase in phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) in the hippocampal CA1 subregion after tGCI. Immunohistochemistry showed that expression of phospho-Akt (Ser473) and phospho-GSK3beta (Ser9) was markedly increased in the vulnerable CA1 subregion, but not in the ischemic-tolerant CA3 subregion. Double staining with phospho-GSK3beta (Ser9) and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed different cellular distributions in the CA1 subregion 3 days after tGCI. Phosphorylation of Akt and GSK3beta was prevented by LY294002, a PI3-K inhibitor, which facilitated subsequent DNA fragmentation 3 days after tGCI. Moreover, transgenic rats that overexpress copper/zinc-superoxide dismutase, which is known to be neuroprotective against delayed hippocampal CA1 injury after tGCI, had enhanced and persistent phosphorylation of both Akt and GSK3beta after tGCI. These findings suggest that activation of the Akt/GSK3beta signaling pathway may mediate survival of vulnerable hippocampal CA1 neurons after tGCI.     

Effects of acute hypovolaemia by furosemide on tracheal transepithelial potential difference and mucus in dogs.

Furosemide is a potent diuretic that affects water transfer across the respiratory epithelium, which is closely related to the transepithelial potential difference (PD). Water is a critical factor that determines mucus transport; an important lung defence mechanism that removes particles and microorganisms from the respiratory system. The aim of the present study was to investigate the acute effects of furosemide and hypovolaemia on tracheal PD and mucus properties. A total of 36 male mixed-breed dogs were submitted to anaesthesia, mechanical ventilation and haemodynamic monitoring. They were randomly assigned to three groups consisting of: a control group, a furosemide (40 mg i.v.) + hypovolaemia group, and a furosemide (40 mg i.v.) + volume replacement group. Tracheal PD and mucus samples were collected at time 0, 1 and 2 h after intervention. Mucus properties were analysed by means of a magnetic microrheometer and in vitro mucociliary transportability on the frog palate. Compared to controls, furosemide decreased PD to intermediate values, and only significantly when associated with hypovolaemia (-13+/-5 and -8+/-2 mV, time 0 and 2 h, respectively). In addition to the direct effect of furosemide, these results indicate that hypovolaemia also affects ion transport in the tracheal membrane. Furosemide and hypovolemia have no acute effects on respiratory mucus properties.     

Angiotensin I-converting enzyme inhibitor improves reactive hyperemia in elderly hypertensives with arteriosclerosis obliterans.

Endothelial function in elderly hypertensive patients with arteriosclerosis obliterans has not been evaluated. We examined whether antihypertensive drugs improve vasodilatory response to reactive hyperemia of the limbs in elderly hypertensive patients (83 +/- 8 [SD] years) without (n=46, 0.9 < or = ankle-brachial pressure index < or = 1.4) and with (n=24) arteriosclerosis obliterans (ankle-brachial pressure index < 0.2). Patients were randomized for treatment with monotherapy of either temocapril (14 with and 26 without arteriosclerosis obliterans) or amlodipine (10 with and 20 without arteriosclerosis obliterans) for 6 months. Blood flows of the forearms and legs were measured by strain-gauge plethysmography. The vasodilatory response to the release of compression of the forearms and thighs at 200 mmHg or 20 mmHg more than systolic blood pressure for 5 min and to sublingual administration of nitroglycerin (0.3 mg) was assessed. The maximum reactive hyperemic flow in 35 legs with arteriosclerosis obliterans was significantly (p < 0.001) decreased compared to the value in legs in the control hypertensive subjects. Moreover, maximum reactive hyperemic flow in the forearms of patients with arteriosclerosis obliterans was significantly (p = 0.002) decreased compared to that in the control subjects. Blood pressure was similarly decreased by treatment with temocapril or amlodipine. Response to nitroglycerin (0.3 mg) was not changed by either drug. Treatment with temocapril significantly improved maximum reactive hyperemic flow of not only the legs and forearms in control hypertensives but also the legs and forearms in patients with arteriosclerosis obliterans, and attenuated the worsening of activity of daily living in these patients, although treatment with amlodipine did not. These results suggest that the angiotensin-converting enzyme inhibitor temocapril has a beneficial effect on endothelial function in elderly patients with arteriosclerosis obliterans.     

Pemphigus Vulgaris Associated with Autoimmune Hemolytic Anemia and Elevated TNFα

A 76-year-old female was admitted with many bullae and erythema on her trunk and extremities. A biopsy specimen showed significant intercellular edema in the lower epidermis and eosinophilic infiltration into the dermis and the epidermis. Immunofluorescent staining revealed the deposition of IgG in the intercellular area of her prickle cells. From these histologic findings and the typical clinical features, we diagnosed her as having pemphigus vulgaris. Examination of her blood revealed that she also suffered from autoimmune hemolytic anemia. Despite intensive treatment with prednisolone, she finally died. This case is of interest because of its rarity and the TNFα detected significantly in the blister fluid of this patient.