A comparative study between preoperative and postoperative pulmonary functions and diaphragmatic movements in congenital craniovertebral junction anomalies

Respiratory dysfunctions in patients with craniovertebral junction (CVJ) anomalies may occur due to compression of brainstem affecting the respiratory centers, and weakening of the muscles of respiration. We assessed pulmonary functions [forced vital capacity (FVC), forced expiratory volume in first second (FEV1), maximum mid-expiratory flow rate (FEF25%-75%), FEV1%], mouth pressures (maximum inspiratory pressure, maximum expiratory pressure), and diaphragmatic movements in 30 patients of CVJ anomalies and compared them with their mean predictive values. These parameters were also assessed in the postoperative period. It was found that the mean values of FVC, FEV1, and FEF25%-75% were significantly lower (P<0.001) than their mean predictive values (2.4+/-0.8 L, 2.0+/-0.7 L, 2.5+/-0.9 L vs. 3.7+/-0.9 L, 3.2+/-0.7 L, and 3.4+/-0.7 L, respectively). In the postoperative period there was significant reduction (P<0.05) in all these parameters (2.2+/-0.8 L, 1.7+/-0.7 L, and 2.1+/-0.8 L, respectively). The postoperative FEV1% was 78.8% compared with the preoperative value of 85.7%. A restrictive pattern of lung disease was observed which persisted in the postoperative period. The postoperative maximum inspiratory pressure and maximum expiratory pressure were comparable to their preoperative values (47.9+/-19.6 and 47.0+/-16.7 cmH2O vs. 42.6+/-17.3 and 43.9+/-18.2 cmH2O, respectively). Similarly, the diaphragmatic movements were also comparable to the preoperative values, both during quiet and deep breathing (13.7+/-3.9 and 38.0+/-9.3 mm vs. 13.8+/-3.9 and 39.0+/-9.1 mm, respectively). There was no improvement of pulmonary functions in the early postoperative period. However, a long-term follow-up is needed to determine subsequent changes of these parameters.     

The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke

Microglia and brain infiltrating macrophages significantly contribute to the secondary inflammatory damage in the wake of ischemic stroke. Here, we investigated whether inhibition of KCa3.1 (IKCa1/KCNN4), a calcium-activated K⁺ channel that is involved in microglia and macrophage activation and expression of which increases on microglia in the infarcted area, has beneficial effects in a rat model of ischemic stroke. Using an HPLC/MS assay, we first confirmed that our small molecule KCa3.1 blocker TRAM-34 effectively penetrates into the brain and achieves micromolar plasma and brain concentrations after intraperitoneal injection. Then, we subjected male Wistar rats to 90 minutes of middle cerebral artery occlusion (MCAO) and administered either vehicle or TRAM-34 (10 or 40 mg/kg intraperitoneally twice daily) for 7 days starting 12 hours after reperfusion. Both compound doses reduced infarct area by ∼50% as determined by hematoxylin & eosin staining on day 7 and the higher dose also significantly improved neurological deficit. We further observed a significant reduction in ED1⁺-activated microglia and TUNEL-positive neurons as well as increases in NeuN⁺ neurons in the infarcted hemisphere. Our findings suggest that KCa3.1 blockade constitutes an attractive approach for the treatment of ischemic stroke because it is still effective when initiated 12 hours after the insult.     

Immunomodulatory and antitumor activity of Aerva lanata ethanolic extract

Cancer is responsible for millions of deaths each year worldwide. Pharmacological intervention with plant-derived products alone or in combination to reverse, suppress, or prevent the cancer progression plays a key role in the fight against this terrible disease. Aerva lanata is an important medicinal plant widely used in traditional systems of medicine like ayurveda and siddha. Ethanolic extract of whole plant of A. lanata exhibited immunomodulatory and antitumor activity. Intraperitoneal administration of five doses of the extract (10?mg/kg body weight) was found to enhance the total WBC count (14,238 cells/mm(3)), bone marrow cellularity (22.33?×?10(6) cells/femur), and number of α-esterase-positive cells (1276 cells/4000 cells). Aerva treatment also showed enhanced proliferation of splenocytes, thymocytes, and bone marrow cells both in the presence and absence of specific mitogens in vitro and in vivo. The number of plaque-forming cells (PFC) in spleen (243.33 PFC/10(6) spleen cells) and circulating antibody titer were also increased (P?相似文献   

Hepatoprotective activity of Musa paradisiaca on experimental animal models

Objective

To investigate the hepatoprotective activity of stem of Musa paradisiaca (M. paradisiaca) in CCl₄ and paracetamol induced hepatotoxicity models in rats.

Methods

Hepatoprotective activity of alcoholic and aqueous extracts of stem of M. paradisiaca was demonstrated by using two experimentally induced hepatotoxicity models.

Results

Administration of hepatotoxins (CCl₄ and paracetamol) showed significant biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with alcoholic extract (500 mg/kg), more significantly and to a lesser extent the alcoholic extract (250 mg/kg) and aqueous extract (500 mg/kg), reduced the elevated levels of the serum enzymes like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and bilirubin levels and alcoholic and aqueous extracts reversed the hepatic damage towards the normal, which further evidenced the hepatoprotective activity of stem of M. paradisiaca.

Conclusions

The alcoholic extract at doses of 250 and 500 mg/kg, p.o. and aqueous extract at a dose of 500 mg/kg, p.o. of stem of M. paradisiaca have significant effect on the liver of CCl₄ and paracetamol induced hepatotoxicity animal models.     

Obatoclax interacts synergistically with the irreversible proteasome inhibitor carfilzomib in GC- and ABC-DLBCL cells in vitro and in vivo

Interactions between the irreversible proteasome inhibitor carfilzomib and the pan-BH3 mimetic obatoclax were examined in germinal center (GC)- and activated B-cell-diffuse large B-cell lymphoma (ABC-DLBCL) cells. Cotreatment with minimally toxic concentrations of carfilzomib (i.e., 2-6 nmol/L) and subtoxic concentrations of obatoclax (0.05-2.0 μmol/L) synergistically increased apoptosis in multiple DLBCL cell lines and increased lethality toward primary human DLBCL but not normal CD34(+) cells. Synergistic interactions were associated with sharp increases in caspase-3 activation, PARP cleavage, p-JNK induction, upregulation of Noxa, and AKT dephosphorylation. Combined treatment also diminished carfilzomib-mediated Mcl-1 upregulation whereas immunoprecipitation analysis revealed reduced associations between Bak and Mcl-1/Bcl-xL and Bim and Mcl-1. The carfilzomib/obatoclax regimen triggered translocation, conformational change, and dimerization of Bax and activation of Bak. Genetic interruption of c-jun-NH(2)-kinase (JNK) and Noxa by short hairpin RNA knockdown, ectopic Mcl-1 expression, or enforced activation of AKT significantly attenuated carfilzomib/obatoclax-mediated apoptosis. Notably, coadministration of carfilzomib/obatoclax sharply increased apoptosis in multiple bortezomib-resistant DLBCL models. Finally, in vivo administration of carfilzomib and obatoclax to mice inoculated with SUDHL4 cells substantially suppressed tumor growth, activated JNK, inactivated AKT, and increased survival compared with the effects of single-agent treatment. Together, these findings argue that a strategy combining carfilzomib and obatoclax warrants attention in DLBCL.