Synthesis of some hetaryl substituted benzofurans of potential antitumor activity

Acetyl-benzo [b] furan [1] reacts with DMF - DMA to give the novel 1-[benzofuran-2-yl]-3-[dimethylamino rpropen-2-one [2]. The reaction of the latter with hydroxylamim: or hydrazine hydrate furnished 5- [benzofuran-2-yl]-isoxazole [3] and 3-[benzofuran-2-yl]-1 H-pyrazole [4], respectively. Also. reaction of2 with various active methylene compounds and hydrazonoyl halides afforded regioselectively the respective 2,3.6- trisllbstituted pyridine [Sa-c] and [pyrazol-4-yl]methanones [10a-t]. respectively. Also. reaction of 10 with hydrazine hydrate afforded the corresponding pyrazolopyriú:lazines [II a-c]. Preliminary screening for the antitumor activity of the synthtsized compounds against the liver carcinoma cell line HEPG-2 has been carried out. The results revealed that the compounds 3. 4 and 13b showed high degree of activity. while the other compounds showed low activity

Synthesis and antimicrobial activity of some substituted 1, 3, 4-oxadiazole and other heterocycles derived from 4, 5-dimethoxy-2-nitrophenyl-thioacetic acid hydrazide

Anumber of substituted oxadiazoles, benzothiazinones and other heterocycles were synthesized from 4, 5-dimethoxy-2-nitrophenylthioacetic acid hydrazide. The structures of the prepared compounds were confirmed via their elemental analysis and the usual physical measurements. The prepared compounds have been screened for their antimicrobial activities against examples from gram positive, gram negative bacteria and fungi. Two of the tested compounds showed high activity comparable with the reference Levofloxacin while the others showed moderate to low activity

Autoimmunity and predictors of autoimmune diseases in the first degree relatives of patients with primary biliary cirrhosis

Primary biliary cirrhosis [PBC] is a chronic autoimmune disease of unknown cause that leads to destruction of intrahepatic ducts leading to ductopenia, fibrosis and ultimate biliary cirrhosis. Autoimmunity and autoimmune diseases were reported in family members of PBC patients. The aim of the present study was to investigate the prevalence of biochemical and immunological abnormalities and autoimmune diseases in first degree relatives [FDR] of patients with PBC. This study included: [1] A female [45 years old] patient diagnosed as having PBC, [2] Five FDR [3 females and 2 males] and [3] Fifteen blood donors [3 females and 12 males] were taken as a control group. Blood samples were taken from all subjects for the detection of nitric oxide [NO], transaminases [AST and ALT], alkaline phosphatase [ALP], total protein and albumin by colorimetric methods. Indirect immunofluorescent techniques were used for the detection of anti-nuclear antibodies [ANA], anti-smooth muscle antibodies [ASMA], anti-actin antibodies [AAA], anti-liver/kidney microsomes antibodies [LKM-I] and anti-mitochondrial antibodies [AMA]. Serum IgM was detected by radial immunodiffusion. Anti-SSA, anti-SSB and IgM rheumatoid factor [IgM RF] were detected by enzyme linked immunosorbent assays. Our PBC patient had a marked increase serum ALP level and a mild elevation in transminases. After treatment, serum ALP level dropped markedly [but still elevated] while the transaminases did not show a remarkable change. A marked elevation was noted in the serum levels of total globulins before and after treatment. A detectable decrease in the level of serum IgM was found after treatment. NO level of our patient was elevated [7 micro moI/L] at presentation while after treatment the level of NO returned to the normal level. AMA titer of our patient was 1/20 which considered a low titer. ANA titer was the same [1/40] before and after treatment. HCV antibodies, HBsAgs and other autoantibodies were absent before and after treatment. The titer of ASMA dropped from 1/160 to 1/40 after treatment. The pattern of these ASMA was the Vessels [V] pattern. In the FDR, the level of NO was elevated in sister-2, son-1 and the daughter. The AST ALT, ALP, total protein and albumin were normal in all subjects. Serum total globulins and IgM were elevated in sister-1, sister -2 and son-1. The ANA titer was 1/40 with a speckled pattern in all FDR. AAA, anti-SSA, anti-SSB, AMA, HBs Ag were negative in all FDR with the exception of sister-2 while had a positive anti-SSB. The ASMA were positive with the same pattern with varying titers. HCV antibodies were positive only in son-1 while was also the only FDR- to have autoantibodies to LKM-1. Sister-1 and sister-2 were diagnosed as a seropositive rheumatoid arthritis [RA] about 2 and 2.5 years after the development of PBC in our patient. The 15 blood donors showed a normal results except subjects 6 and 11 who had ASMA with a titer of 1/20 and subject 7 who had a positive ANA [titer l/40]. An autoimmune disease [RA] developed in two sisters of the PBC patient. Predictors of autoimmune diseases like elevated NO, LKM-1 and SSB antibodies are common in the FDR of a patient with PBC. Follow up of such subjects with these autoimmune predictors is recommended

Anti cyclic citrullinated peptide antibodies in IgM rheumatoid factor positive patients: a new insight

The presence of IgM rheumatoid factor [IgM RF] is one of the clinical criteria for the diagnosis of rheumatoid arthritis [RA]. The cutoff point of IgM RF assays is usually based on a reference level obtained from normal subjects in the same population as the patients. However, raising the cutoff values increases the specificity of RF testing. The present study was undertaken to investigate this observation with the help of anti cyclic citrullinated peptide [CCP] antibodies to be of potential diagnostic value. Seventy six patients were chosen with arthritis and IgM RF titers > 20 units/ml. Subsequently, patients were classified according to their IgM RF titers: patients with titers 40 units/ml [group B] and patients [selected from group B] with titers >120 units/ml [group C]. Twenty one RA patients with IgM RF negative and positive anti CCP antibodies were also included in this study. In all serum samples, IgM RF, anti CCP, hepatitis C virus antibodies [HCV], anti-Smith and anti-ribonucleoprotein [anti-RNP] antibodies were determined by ELISA. PCR analysis was performed for all patients with positive HCV antibodies. Antinuclear antibodies [ANA] and anti-dsDNA were determined by indirect immunofluorescence. In patients of groups A, B and C, RA was detected in 28.6, 80.5 and 83.3% of all patients, respectively. Anti CCP antibodies detected RA in 22.85, 75.6 and 77.8% of all patients in groups A, B and C, respectively. IgM RF positive non RA patients were diagnosed in 71.4, 19.5 and 16.7% among all patients included in group A, B and C, respectively. In group A, anti CCP antibodies correctly classified 24/25 [96%] of patients with false positive IgM RF as non RA patients, they were positive in only one patient with rhupus. Anti CCP antibodies were positive in 2.8, 4.9 and 11.1% in non RA patients among all patients in group A, B and C, respectively. Anti CCP antibodies were present in 80, 93.9 and 93.3% of RA patients in groups A, B and C, respectively. The overall presence of anti CCP in seropositive RA patients was 90.6%. Kappa statistics showed an excellent agreement between IgM RF and anti CCP for the serodiagnosis of RA. Among the non RA patients of group A, it was found that 9/25 [36%] of patients diagnosed as having HCV infection. Anti CCP antibodies were negative in all HCV patients. Low positive titers of anti CCP antibodies were more prevalent [76.2%] in patients with seronegative RA than in patients with seropositive RA [17.9%]. Results demonstrated that: [1] anti CCP antibodies correctly classified about 24/25 [96%] of patients with false positive IgM RF [< 40 units/ml] as non RA, [2] high titers of IgM RF [>120 units/ml] are of similar high specificity to anti CCP antibodies and [3] anti CCP antibodies are able to differentiate between patients with HCV infection associated with arthritis and patients with RA

Role of deliberate creation of control enterocutaneous fistula in patients of abdominal tuberculosis with perforation of small bowel and matted small intestine

To study the results after forming the controlled enterocutaneous fistula in the patient of abdominal tuberculosis with matted and perforated small bowel. Design, place and duration of study This study based on therapeutic trial and conducted in one and half years from january1999 to june2001 at Mayo Hospital, Lahore. All these 20 patients either operated in emergency or on elective list were malnourished, toxic and their operative findings were almost the same, these patients had extensively matted, friable and perforated gut. In these patients it was technically not possible to perform some definite procedure like right haemecolectomy or ileostomy with out increasing the morbidity or mortality. Under these circumstances, minimal surgical procedure which can be life saving is to oppose the anterior abdominal wall to the perforation and thus create a controlled enterocutaneous fistula. In 11 patients fistula closed on its own and in eight patients fistula remained patient and needed re-exploration and repair. This new method of treatment has yielded excellent results. We were able to cure the disease with no mortality. It is recommended that in cases of TB peritonitis with perforation and matted gut making of a controlled enterocutaneous fistula saves the life of the patient

Chemical composition of urinary stones in Rahim Yar Khan and adjacent districts of Sindh and Baluchistan

To find out the constituents of the urinary stones, so that preventive measures would be taken against recurrence. A total No. of 200 consecutive patients with upper urinary tract calculi, that were operated in the urology and general surgical wards of Sh. Zayed Hospital Rahim Yar Khan were included in the study. In addition to Rahim Yar Khan the patients also came from adjacent districts of Sindh and Baluchistan. Qualitative Chemical analysis was carried out using Merchognost [Germany] urinary calculi analysis kit. All the tests were performed according to the instruction of manufacturers of the kit. Stone samples were collected from 200 patients, out of these 138 [69%] were male and 62 [31%] of patients were female with male to female ratio 2.2:1 age range was between 9-72 years. Results of stone analysis indicate that calcium oxalate is the most common ingredient found in 100% of the stone samples. In 83% of patients it was found mixed with other varieties of stones while in 17% samples it was seen in pure form. Uric acid was the second most common ingredient seen in 73% of patients mixe d with calcium oxalate and magnesium ammonium phosphate but it was not found as pure form. Magnesium Ammonium phosphate found in 13% of stones samples in mixed form only, not as isolated stone

Frequency of benign breast diseases in female patients presenting with breast lumps - a study at sir Ganga Ram Hospital, Lahore

To determine the frequency of benign breast diseases in female patients in our setup. Prospective descriptive study. The study was carried on female patients presenting at surgical out door of Sir Ganga Ram Hospital, Lahore during one year i.e. January 2001 to January 2002. Two hundred female patients presenting with breast lumps at surgical out door of Sir Ganga Ram Hospital, Lahore during one year were studied. All the patients were examined clinically with special emphasis on breast, axilla and supra clavicular fossae. Basic laboratory investigations including blood complete examination, urine complete examination and chest X -ray were done for all the patients. Breast imaging and FNAC of lumps were also done. Final diagnosis was based upon histological examination of the tissues biopsied from the lump. After collecting data, written in proforma, window SPSS software was used to analyze the results. This study shows a high f requency of fibroadenoma [45%] in Pakistani females. Fibrocystic disease is second in frequency and accounts for 36% patients.8% patients had intraductal papilloma and three percent suffered from duct ectasia.5% patients had other conditions related to breast including two patients presenting with pre histological diagnosis of fibrocystic disease who turned out to be malignant after histopathology. Most of the patients had age range of 20-29 years. Fibroadenoma is the commonest of all benign breast diseases in Pakistani women. Fibrocystic change is the second in this regard. Benign lesions of the breast can resemble its carcinoma on clinical examination