Pd(II) Complexes of Chiral Proline-Derived Ligands: Application for Dynamic Thermodynamic Resolution of α-Amino Acids and Their Antibacterial Activities.

Novel type of Pd(II) complexes have been synthesized under operationally simple and convenient conditions and applied in the dynamic thermodynamic resolution of racemic N,C-unprotected α-amino acids. After rapid hydrolysis, these Pd(II) complexes produced the corresponding α-amino acids in satisfactory yields and enantioselectivities, accompanied by the recyclable proline-derived ligand. In addition, the method can be readily applied for S/R interconversion to obtain unnatural (R)-α-amino acids from readily available (S)-α-amino acids. Furthermore, biological assays showed that Pd(II) complexes (S,S)-3i and (S,S)-3m exhibited significant antibacterial activities similar to vancomycin, which may represent promising lead structures for further development of antibacterial agents.

Cu(II) Complexes with Proline-Derived Schiff Base Ligand: Chemical Resolution of N,C-Unprotected α-Amino Acids and Their Antibacterial Activity.

An operationally simple and convenient resolution method via Cu(II) complexes was reported, efficiently providing valuable enantiopure N,C-unprotected α-amino acids. This protocol features synthetically attractive yields and a stereochemical outcome, using a recyclable Schiff base ligand and inexpensive easily accessible metal copper salts. These novel Cu(II) complexes can be obtained in an enantiopure state by means of column chromatography or recrystallization. Furthermore, all the Cu(II) complexes were evaluated for their antibacterial activities. Among them, complexes (S,2S)-3a, (S,2S)-3g, and (S,2S)-3o showed significant antibacterial activities against Staphylococcus aureus Mu50. Further biological evaluation indicated that they were effective against most of Gram-positive bacteria. It is the first study on the biological activities of transition metal complexes with this type of proline-derived Schiff base ligand.

Modulation of MRSA virulence gene expression by the wall teichoic acid enzyme TarO.

Phenol-soluble modulins (PSMs) and Staphylococcal protein A (SpA) are key virulence determinants for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), an important human pathogen that causes a wide range of diseases. Here, using chemical and genetic approaches, we show that inhibition of TarO, the first enzyme in the wall teichoic acid (WTA) biosynthetic pathway, decreases the expression of genes encoding PSMs and SpA in the prototypical CA-MRSA strain USA300 LAC. Mechanistically, these effects are linked to the activation of VraRS two-component system that directly represses the expression of accessory gene regulator (agr) locus and spa. The activation of VraRS was due in part to the loss of the functional integrity of penicillin-binding protein 2 (PBP2) in a PBP2a-dependent manner. TarO inhibition can also activate VraRS in a manner independent of PBP2a. We provide multiple lines of evidence that accumulation of lipid-linked peptidoglycan precursors is a trigger for the activation of VraRS. In sum, our results reveal that WTA biosynthesis plays an important role in the regulation of virulence gene expression in CA-MRSA, underlining TarO as an attractive target for anti-virulence therapy. Our data also suggest that acquisition of PBP2a-encoding mecA gene can impart an additional regulatory layer for the modulation of key signaling pathways in S. aureus.

Chronic pancreatitis-induced compressed relative stenosis of the distal common bile duct.

BACKGROUND: Fibrosis and enlargement of chronic pancreatitis (CP) can cause biliary stenosis, in which fixed circular stenosis is the common type, by compressing the intrapancreatic portion of the common bile duct. Another type of distal bile duct stenosis is compressed relative stenosis, in which the common bile duct walks along the back of the pancreas partially. METHODS: Thirty patients with dilation of the proximal common bile duct (diameter > or = 15 mm) caused by CP underwent overall and systemic exploratory operation at our hospital. All of the patients were followed up for 3.5 to 15 years, averaging 8.5 years. RESULTS: The intrapancreatic portion of the common bile duct was found to walk along the back of the pancreas, and its anterior wall was compressed flat by enlarged pancreas, but the posterior wall showed a good flexibility because there was no pancreas covering. Bake's dilators bigger than No.6 (diameter > or = 4 mm) and No.14 urinary catheter could pass through the distal common bile duct after the posterior wall was separated. Roux-en-Y choledochojejunostomy was performed for 4 patients, and T-tube drainage was carried out for the remaining 26 patients. All of the patients were followed up but 2 were lost. Only 2 patients underwent choledochojejunostomy 3 years after T-tube drainage because of repeated acute pancreatitis attack, and others were normal. CONCLUSIONS: Compressed relative stenosis of the distal common bile caused by CP is a clinical sign, and its diagnosis mainly depends on surgical findings. Most patients can be treated by separating the posterior wall of the pancreas and T-tube drainage as well, but to patients with recurrent CP, choledochojejunostomy may be a feasible alternative.

Clinical analysis of pericardial devascularization by preserving vagus trunks in 42 patients with portal hypertension.

Pericardial devascularization (PD) is less of a burden and provides better bleeding control to patients compared to shunt procedures, and so has been widely used in portal hypertension in China. However, because the vagus trunks are interrupted during surgery, patients easily suffer from postoperative stomach adynamia. Based on our understanding from autopsy of the path of vagus trunks along the distal oesophagus, we designed the operative procedure of PD by preserving vagus trunks (PDPVT) to treat portal hypertension. Between May 1991 and January 2003, patients with portal hypertension were treated surgically using PDPVT (n = 42), single PD (n = 32), or PD with pyloroplasty (PD+PP; n = 16). Operative mortality was 2.4% in the PDPVT group and 6.3% in both the PD and PD+PP groups (p > 0.05). The postoperative rebleeding rate was 9.5% in the PDPVT group and 12.5% in both the PD and PD+PP groups (p > 0.05). There were no differences in operative time and estimated blood loss between the three groups (p > 0.05). The recovery time for gastroenteric function was shorter with PDPVT (mean, 3.5 days) than with PD (mean, 5.7 days) and PD+PP (mean, 4.2 days; p < 0.02). Incidences of early satiety and enterogastric reflux were significantly lower in the PDPVT group (both 4.8%) than in the PD group (46.9% and 18.8%) and PD+PP group (12.5% and 100%; p < 0.005). Incidences of retention of gastric juice, diarrhoea and late gallstones were 12.5%, 15.6% and 7.1%, respectively, in the PD group, and 12.5%, 18.8% and 6.3%, respectively, in the PD+PP group, but none of these were observed in the PDPVT group. Since it preserves vagus trunks, PDPVT can maintain normal stomach dynamics and physiological function of hepatobiliary and gut systems better than PD and PD+PP, thus reducing incidences of postoperative complications. Thus, PDPVT is superior to PD and PD+PP in the treatment of portal hypertension.

Peripheral blood cell variations in cirrhotic portal hypertension patients with hypersplenism.

OBJECTIVE: To explore peripheral blood cell variations in hepatic cirrhosis portal hypertension patients with hypersplenism. METHODS: Clinical data of 322 hypersplenism patients with decreased peripheral blood cells, admitted with cirrhotic portal hypertension, was retrospectively studied over the last 17 years. RESULTS: In 64% (206/322) of patients, more than 2 kinds of blood cell were decreased, including 89 cases of pancytopenia (43.2%), 52 cases of WBC + PLT decrease (25.2%), 29 cases of RBC + PLT decrease (14.1%), and 36 cases of WBC + RBC decrease (17.5%); in 36% (116/322) of patients, single type blood cell decrease occurred, including 31 cases of PLT decrease (26.7%), 29 cases of WBC decrease (25%) and 56 cases of RBC decrease (48.3%). Of 227 routine bone marrow examinations, bone marrow hyperplasia was observed in 118 cases (52.0%), the remainder showed no hyperplasia. For the distinct scope and extent of peripheralblood cell decreases, preoperative blood component transfusions were carried out, then treated by surgery, after whole group splenectomy, the peripheral blood cell count was significantly higher (P<0.05). CONCLUSIONS: Of portal hypertensive patients with splenomegaly and hypersplenism, 64% have simultaneous decrease in various blood cells, 36% have decrease in single type blood cells, 52% of patients have bone marrow hyperplasia. A splenectomy can significantly increase the reduction of peripheral blood cells.

[Historical review of Portal Hypertension].

It has been more than 100 years since the nomenclature Portal Hypertension was put forward, during which the treatment of Portal Hypertension in medical circles experienced a gradual perfection. Reviewing the developmental progress can help to improve the treatment of Portal Hypertension.

[Retrospecting the history of intestinal obstructions].

Intestinal obstruction is one of the common and frequently encountered diseases, the treatment of which has a long and tortuous history with a set of valid therapeutic methods accumulated. When a large segment of necrotic intestine, for instance, is to be removed, how do you maintain the patient's nutrition to protect his/her health. The effect of transplant of intestine for a critical intestinal case is even worse than that of the kidney, liver transplants. To solve this problem demands long and indefatigable endeavor. The goal of this article is to review its history, so as to explore the way of thinking and shed some light on its future studies.

[Historical changes of diagnostic methods for intestinal obstruction].

OBJECTIVE: Abstract Intestinal obstruction is one of the earliest diseases known by humanity with its diagnosis experiencing a long course of history, achieving full-grown improvement, attracting worldwide attention. However, there are also some issues worthy of investigation. For example, the diagnosis of strangulated intestinal obstruction is still a challenge; The rate of misdiagnosis is 37% -50%, etc. Thus, long-term efforts may be still needed to solve these problems.

Gastroduodenal ulcer treated by pylorus and pyloric vagus-preserving gastrectomy.

AIM:To evaluate the curative effect of pylorus and pyloric vagus-preserving gastrectomy (PPVPG) on peptic ulcer.METHODS:Treating 132 cases of GU and DU with PPVPG, and comparative studies made with 24 cases treated with Billroth II (B II ) and 20 cases with Billroth I(BI); advantages and shortcomings evaluated.RESULTS:Not a single death after PPVPG. No recurrence of the disorder in the subsequent follow-up for an average of 6.5 years. Curative effect (visik II & I) 97.7%. Acidity reduction similar to that found in B II and BI, but 97.7% of the B II and all BIcases having more than second degree intestinal fluid reflux, in contrast to 7.1% in PPVPG cases. Dumping syndrome occurred in the B II and BI cases, none in PPVPG cases. With regard to gastric emptying, food digestion, absorption, body weight and life quality, PPVPG proved to be superior to Billroth procedure.CONCLUSION:PPVPG has the advantages of conventional Billroth gastrectomy in reducing acid, removing ulcer focus, and at the same time preserves the pylorus and pyloric vagus for maintaining the normal gastric physiological function.Dumping syndrome,intestinal fluid reflux and other complications of conventional gastrectomy may be avoided.