Synaptic loss and gliosis in the nucleus tractus solitarii with streptozotocin-induced Alzheimer's disease.

Obstructive sleep apnea is highly prevalent in Alzheimer's disease (AD). However, brainstem centers controlling respiration have received little attention in AD research, and mechanisms behind respiratory dysfunction in AD are not understood. The nucleus tractus solitarii (nTS) is an important brainstem center for respiratory control and chemoreflex function. Alterations of nTS integrity, like those shown in AD patients, likely affect neuronal processing and adequate control of breathing. We used the streptozotocin-induced rat model of AD (STZ-AD) to analyze cellular changes in the nTS that corroborate previously documented respiratory dysfunction. We used 2 common dosages of STZ (2 and 3 mg/kg STZ) for model induction and evaluated the early impact on cell populations in the nTS. The hippocampus served as control region to identify site-specific effects of STZ. There was significant atrophy in the caudal nTS of the 3 mg/kg STZ-AD group only, an area known to integrate chemoafferent information. Also, the hippocampus had significant atrophy with the highest STZ dosage tested. Both STZ-AD groups showed respiratory dysfunction along with multiple indices for astroglial and microglial activation. These changes were primarily located in the caudal and intermediate nTS. While there was no change of astrocytes in the hippocampus, microglial activation was accompanied by a reduction in synaptic density. Together, our data demonstrate that STZ-AD induces site-specific effects on all major cell types, primarily in the caudal/intermediate nTS. Both STZ dosages used in this study produced a similar outcome and can be used for future studies examining the initial symptoms of STZ-AD.

Decreased excitability of locus coeruleus neurons during hypercapnia is exaggerated in the streptozotocin-model of Alzheimer's disease.

The locus coeruleus (LC) is a pontine nucleus important for respiratory control and central chemoreception. It is affected in Alzheimer's disease (AD) and alteration of LC cell function may account for respiratory problems observed in AD patients. In the current study, we tested the electrophysiological properties and CO2/pH sensitivity of LC neurons in a model for AD. Sporadic AD was induced in rats by intracerebroventricular injection of 2 mg/kg streptozotocin (STZ), which induces behavioral and molecular impairments found in AD. LC neurons were recorded using the patch clamp technique and tested for responses to CO2 (10% CO2, pH = 7.0). The majority (~60%) of noradrenergic LC neurons in adult rats were inhibited by CO2 exposure as indicated by a significant decrease in action potential (AP) discharge to step depolarizations. The STZ-AD rat model had a greater sensitivity to CO2 than controls. The increased CO2-sensitivity was demonstrated by a significantly stronger inhibition of activity during hypercapnia that was in part due to hyperpolarization of the resting membrane potential. Reduction of AP discharge in both groups was generally accompanied by lower LC network activity, depolarized AP threshold, increased AP repolarization, and increased current through a subpopulation of voltage-gated K+ channels (KV). The latter was indicated by enhanced transient KV currents particularly in the STZ-AD group. Interestingly, steady-state KV currents were reduced under hypercapnia, a change that would favor enhanced AP discharge. However, the collective response of most LC neurons in adult rats, and particularly those in the STZ-AD group, was inhibited by CO2.

Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation.

A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium.

Long-term follow-up of chronic hepatitis B after the emergence of mutations in the hepatitis B virus polymerase region.

Treatment of chronic hepatitis B has been greatly improved by the use of lamivudine, but mutations occur in the polymerase region of hepatitis B virus (HBV) and lamivudine-resistant mutants frequently develop. The emergence of lamivudine-resistant strains of HBV is a problem for treating chronic hepatitis B using lamivudine. We observed biochemical and virological changes in 15 patients with chronic hepatitis B for a median period of 29 months (range: 4-42 months) after the emergence of lamivudine-resistant mutants of HBV. Patterns of mutation of the polymerase gene were examined by sequencing the LLAQ motif in domain B and the YMDD motif in domain C. Exacerbation of liver dysfunction occurred in 14 (93.3%) of the 15 patients at a median of 4 months after the emergence of mutations. However, exacerbation of liver dysfunction was observed only in four patients (26.7%) at the time of appearance of the first mutations and in 80.0% of the patients at the time of appearance of the second mutations. Increase in serum alanine aminotransferase (ALT) levels was significantly greater at the time of appearance of second mutations (P = 0.0096). In most cases, wild-type HBV was mutated with the substitution of only rtM204I at first, and rtL180M/M204I mutations and then rtL180M/M204V mutations subsequently appeared. Further mutations of the polymerase region caused clinical deterioration. Thus as mutations emerge in the polymerase region, the clinical outcome deteriorates. Thus, monitoring the patterns of mutation of the polymerase gene is useful when using lamivudine for treating HBV.

Intraluminal tumor of the common bile duct as a metastasis of renal cell carcinoma.

A 57-year-old woman was admitted for evaluation of liver dysfunction. A physical examination revealed jaundice and a left abdominal mass, which was diagnosed as being a large renal tumor. Cholangiography showed a smooth filling defect 1 cm in diameter at the common bile duct. Left nephrectomy, and resection of the common bile duct were performed. The pathological diagnosis was metastasis of the common bile duct wall resulting from renal cell carcinoma. Metastatic common bile duct tumors are extremely rare. However, it is important to consider that this is one of the causes of obstructive jaundice.

[Non-Hodgkin's lymphoma presenting as a soft tissue tumor in the connective tissue at the thigh].

A 62-year-old man visited our hospital in July 1993, because of a right thigh mass which had grown gradually since two years previously. Physical examination revealed that the mass at the right thigh region, was elastic soft and about 15 x 10 cm in diameter, without regional lymph node swelling. An ultrasound study showed a hypoechogenic and mesh patterned mass. MRI revealed that the tumor was well defined from subcutaneous adipose tissue and skeletal muscle, indicating that it arose in connective tissue. Angiography demonstrated diffuse hypervascularization of the tumor, and Gallium scintigraphy showed remarkable accumulation at the tumor. Serum IgM was increased, which was proven to be an monoclonal hypergammopathy (IgM, lambda). Histological examination of a biopsied specimen obtained from the thigh mass revealed B cell lymphoma, lymphoplasmacytic cell type. The patient achieved a complete remission after surgical treatment following radiation and combination chemotherapy.

Estudos sobre a histologia do leproma por meio da coloração vital

Um de nos praticou (Gujo) a injeção dita de azul de toluidina em um nodulo sem obter a coloração vital, por ser fraca a diluição do corante, ou a injeção não ter atingido a massa do nodulo.O carmin difundia-se dificilmente no nódulo, sendo por isso precária a infiltração do tecido apezar das injeções repetidas.Daí a necessidade desse grande numero de injeções para obter a coloração vital do tecido leprotico. A tinta da China, ao contrario, era bem difusivel. E por isso julgamos bastar uma injeção unica para obter impregnação das celulas em intensidade e numero satisfatorios. Desconhece-se a causa dessa diferente defusibilidade. De acordo com as nossas pesquisas o tecido leprotico é formado de celulas capazes de fixar os corantes, seja o carmin ou a tinta da China. Logares havia onde todas as celulas do granuloma fixavam as pariculas de carvão. Em certos pontos, porém, não havia fixação, tanto nos preparados com carmin, como nos de tinta da China. Entre dois extremos havia porem, todas as formas de transição. Essas variações da coloração vital são inevitaveis na impregnação local, em que o nodulo não se infiltra uniformemente, como na injeção intra-venosa. Desse modo a fixação do corante so pode dar-se no logar em que o liquido se difundiu bem. No que concerne ás celulas do granuloma, tratam-se de celulas epitelioides e de celulas de Virchow, fixando tanto o carmin como o carvão, fora porém da espuma e dos vacuolos do citoplasma. As caracteristicas do histiocito são a capacidade de fixar materias dissolvidas e corpusculares e a fagocitose, propriedades que as nossas pesquisas demonstraram existir nas celulas epitelioides leprosas e nas celulas de Virchow.Goldmann, o primeiro a identificar as celulas pirrolicas do tecido conjuntivo frouxo, com os histiocitos e estes com o macrofago de Metschnikoff e o clasmatocito de Ranvier, é de opinião que as celulas pirrolicas são elementos conjuntivos caracterisados pela coloração vita. Sabe-se hoje, graças aos trabalhos de Kiyono, que as celulas conjuntivas comportam-se positivamente em face da coloração vital uma vez que os fibroblastos fixam alguns granulos. Nas injeções diretas de carmin no tecido conjuntivo frouxo as celulas conjuntivas em repouso fixam algum carmin, menos porem de que a bela coloração dos histiocitos. Nessas celulas, porem havia bacilos. O gráo de fixação era comparativamente menor nas celulas epitelioides e de Virchow, do que nos histiocitos.De acordo com as nossas descrições.