NF-κB in the regulation of epithelial homeostasis and inflammation

The IκB kinase/NF-κB signaling pathway has been implicated in the pathogenesis of several inflammatory diseases. Increased activation of NF-κB is often detected in both immune and non-immune cells in tissues affected by chronic inflammation, where it is believed to exert detrimental functions by inducing the expression of proinflammatory mediators that orchestrate and sustain the inflammatory response and cause tissue damage. Thus, increased NF-κB activation is considered an important pathogenic factor in many acute and chronic inflammatory disorders, raising hopes that NF-κB inhibitors could be effective for the treatment of inflammatory diseases. However, ample evidence has accumulated that NF-κB inhibition can also be harmful for the organism, and in some cases trigger the development of inflammation and disease. These findings suggested that NF-κB signaling has important functions for the maintenance of physiological immune homeostasis and for the prevention of inflammatory diseases in many tissues. This beneficial function of NF-κB has been predominantly observed in epithelial cells, indicating that NF-κB signaling has a particularly important role for the maintenance of immune homeostasis in epithelial tissues. It seems therefore that NF-κB displays two faces in chronic inflammation: on the one hand increased and sustained NF-κB activation induces inflammation and tissue damage, but on the other hand inhibition of NF-κB signaling can also disturb immune homeostasis, triggering inflammation and disease. Here, we discuss the mechanisms that control these apparently opposing functions of NF-κB signaling, focusing particularly on the role of NF-κB in the regulation of immune homeostasis and inflammation in the intestine and the skin.     

Ofloxacin and ciprofloxacin in the treatment of sexually-transmitted diseases]

A complex clinico-laboratory++ examination and treatment were made of 76 women with inflammatory processes in the urogenital tract. Gonorrhea, trichomoniasis, chlamydiosis and Ureaplasma infection were detected in 60, 31.4, 41 and 14 per cent of the cases, respectively. There were affections of the rectum by gonococci, chlamydia, ureaplasmas and Trichomonas in 55, 32, 10.6 and 6.6 per cent of the cases, respectively. The frequency of chlamydia in the oropharynx amounted to 30 per cent whereas gonococci and ureaplasma were less frequent i.e. 9 and 1.2 per cent, respectively. The combination of the above pathogens in the rectum were the following: gonococci and chlamydia (15 per cent of the cases), gonococci, chlamydia and Trichomonas (7.3 per cent), gonococci and ureaplasma (7.3 per cent), ureaplasma and chlamydia (7.8 per cent). In the throat the association of gonococci and chlamydia was detected in 3.7 per cent of the cases. It should be indicated that the signs of sex-transmitted diseases were few, which required careful clinico-laboratory examination of the extragenital foci in the patients with inflammatory urogenital diseases. Ofloxacin showed a high efficacy in the treatment of patients with gonorrhea and ureaplasmosis. Its use in treatment of chlamydiosis proved inexpedient while ciprofloxacin was effective in the treatment of the infection.     

ACUTE GALLBLADDER DISEASE—Experiences with 103 Consecutive Cases

One hundred and three cases of acute cholecystitis in patients ranging in age from 19 to 88 years were reviewed. Operation was done in all cases. Seventy per cent of the patients were women.Primary cholecystectomy was done in 72.8 per cent of the series. Primary cholecystostomy was performed in the remainder, and one-fourth of these patients had a secondary cholecystectomy. No specific time, with relation to interval after onset of symptoms, was chosen for operation.Jaundice was present in 14.5 per cent of patients at the time of admittance to hospital. Serum amylase was above normal in five of 27 patients on whom this determination was carried out. All five were women.The gallbladder was perforated in 13 cases. Common duct exploration was done in 25 cases and in 12 of them stones were found.The morbidity rate for the series was 11.6 per cent; the mortality rate 9.7 per cent.     

PRIMARY CARCINOMA OF THE GALLBLADDER—Review of 173 Cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females.Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease.All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy.The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred.Gallstones were found in 79.8 per cent of the cases.     

Primary carcinoma of the gallbladder; review of 173 cases

One hundred seventy-three cases of primary carcinoma of the gallbladder were analyzed. In the group studied they made 2.11 per cent of all malignant tumors found at autopsy and were found in 1.89 per cent of all cases in which operation was done on the biliary tract. There was no appreciable change in the incidence of this tumor at autopsy during the period studied (1918-1948) at the Los Angeles County Hospital. Sixty-eight per cent of the cases were in females. A particularly high incidence was noted in Mexican females. Upper abdominal pain, loss of weight, nausea and vomiting, jaundice, and palpable mass or enlarged liver were the most common clinical features. Approximately one-third of the patients in whom the lesion was found at operation and one-fifth of all the patients whose records were studied had a history of chronic gallbladder disease. All but two of the 38 patients operated on were dead or had clinical recurrence within two years. One was alive and well 12 years after cholecystectomy. The most common gross appearance, particularly at autopsy, was a large tumor mass replacing the gallbladder and radiating to nearby organs, particularly the liver. In about one-third of the cases the tumor was grossly limited to the gallbladder. Polypoid tumors occurred in only about 10 per cent of the cases and most of the tumors were diffusely growing adenocarcinoma. Perforation appeared in nine cases, usually with fistula to the gastrointestinal tract. All of the tumors were histologically adenocarcinoma, usually of simple glandular structure. No purely squamous cell growth occurred. Gallstones were found in 79.8 per cent of the cases.     

Vasculitis: mechanisms involved and clinical manifestations

Systemic vasculitis, an inflammatory necrotizing disease of the blood vessel walls, can occur secondary to autoimmune diseases, including connective tissue diseases. Various pathogenic mechanisms have been implicated in the induction of vasculitis, including cell-mediated inflammation, immune complex-mediated inflammation and autoantibody-mediated inflammation. This inflammatory activity is believed to contribute to accelerated atherosclerosis, and also leads to increased risk for cardiovascular events in patients with rheumatoid arthritis and systemic lupus erythematosus. Endothelial cell activation is a common pathogenic pathway in the systemic vasculitis associated with rheumatoid arthritis and systemic lupus erythematosus, with elevated levels of endothelin-1 potentially inducing vascular dysregulation.     

Reliability of cytologic typing of lung cancer.

In a prospective study of 111 cases of lung cancer, cytopathologic diagnoses were compared with histologic diagnoses. In 77.5 per cent of the cases, histopathologic diagnoses were in concurrence with cytopathologic diagnoses. The discrepancies occurred mainly in poorly differentiated adeno and epidermoid carcinoma. Well differentiated adeno and epidermoid carcinoma were cell typed with 100 per cent accuracy and small cell carcinoma with 90 per cent accuracy.     

X-ray and ultrasonic diagnosis of noninflammatory benign diseases of the gallbladder]

The author analyzes the results of x-ray (cholecystography) and ultrasonic examinations carried out in patients with noninflammatory benign diseases of the gallbladder (71 with cholesterosis and 28 with adenomyomatosis). X-ray and ultrasonic symptoms of these conditions are presented and the diagnostic potentialities of both methods in the detection of such diseases assessed. The author considers ultrasonic scanning the method of choice for the diagnosis of any forms of gallbladder cholesterosis, whereas an x-ray examination appears to be informative only in a polypous form of the disease. X-ray contrast examination is preferable for the recognition of gallbladder adenomyomatosis, for it presents a clear-cut pattern characteristic of each form of this condition, whereas ultrasonic symptoms of such involvement are nonspecific.     

Immunoresolvents in asthma and allergic diseases: Review and update

Asthma and allergic diseases are inflammatory conditions developed by excessive reaction of the immune system against normally harmless environmental substances. Although acute inflammation is necessary to eradicate the damaging agents, shifting to chronic inflammation can be potentially detrimental. Essential fatty-acids-derived immunoresolvents, namely, lipoxins, resolvins, protectins, and maresins, are anti-inflammatory compounds that are believed to have protective and beneficial effects in inflammatory disorders, including asthma and allergies. Accordingly, impaired biosynthesis and defective production of immunoresolvents could be involved in the development of chronic inflammation. In this review, recent evidence on the anti-inflam]matory effects of immunoresolvents, their enzymatic biosynthesis routes, as well as their receptors are discussed.     

Use of cefoperazone in clinical practice]

The bacteriological and clinical efficacy and side effects of cefoperazone were studied in 45 patients with severe and moderate purulent inflammatory diseases. The study showed that its bacteriological and clinical efficacy was high in cases with peritonitis, cholecystitis, respiratory and urinary infections, as well as those of the eye and soft tissues. The general clinical efficacy amounted to 95.6 per cent. The number of the side effects was insignificant. This made it possible to recommend the use of cefoperazone in the therapy of many purulent inflammatory diseases, as well as in empirical therapy.     

Combination of two danger signals (microorganisms and xenobiotics) is the principal cause of activation of chronic inflammatory processes

Chronic inflammatory diseases are of long duration, during which remissions alternate with exacerbations. Until recently, it was believed that the occurrence and activation of a chronic inflammatory process is caused by one danger signal, usually by microorganisms. Taken together, our own and the published data show that the activation of an inflammatory process is associated with the accumulation of macrophages in an inflammatory focus and their subsequent hyperactivation as a result of the combination of two danger signals??microorganisms and xenobiotics.     

Characteristics of the antibiotic sensitivity of nitrofuran--resistant Gram-negative bacteria of clinical origin]

494 persons with various purulent inflammatory diseases were examined. Gram-negative nitrofuran resistant organisms isolated from the clinical material were found in 22.9 per cent of the cases. Representatives of Enterobacteriaceae, Klebsiella-Enterobacter-Serratia (26.8 per cent), Proteus-Providencia (16.8 per cent) and E. coli-Arizona-Citrobacter (16.1 per cent) predominated. Pseudomonas (32.1 per cent) and Acinetobacter (5.3 per cent) predominated among the aerobic gram-negative bacteria. Sensitivity of 131 strains to 10 chemotherapeutic drugs was determined. 60.4 per cent of the aerobic and 44.2 per cent of the Coli bacteria had multiple drug resistance (to 5 and more drugs). The organisms isolated from the urine and wound excretion were most resistant. Representatives of Pseudomonas and Klebsiella-Enterobacter predominated among the polyresistant cultures. High sensitivity of the isolates to gentamicin, carbenicillin and nalidixic acid was noted.     

Critical involvement of the chemotactic axis CXCR4/stromal cell-derived factor-1 alpha in the inflammatory component of allergic airway disease

Stromal cell-derived factor-1alpha/beta (SDF-1alpha/beta) is phylogenetically a primitive chemokine widely expressed in a variety of tissues and cell types. This expression is detectable in the absence of stimuli provided by bacterial or viral infections and allergic or autoimmune disorders. Based on these and other findings, SDF-1alpha has not been considered an inflammatory chemokine, but, rather, has been believed to be involved in certain homeostatic processes, such as leukocyte recirculation. SDF-1alpha is a potent chemoattractant for lymphocytes and monocytes that mediates its activity via the chemokine receptor CXCR4. Study of the role of SDF-1alpha/CXCR4 in vivo during inflammation has been limited by the fact that transgenic mice that have been made deficient in either molecule die early in life due to developmental defects. The present study was aimed at evaluating the functional relevance of the SDF-1alpha/CXCR4 axis during an inflammatory process. Neutralizing Abs to CXCR4 reduced lung eosinophilia (bronchoalveolar lavage fluid and interstitium) by half, indicating that CXCR4-mediated signals contribute to lung inflammation in a mouse model of allergic airway disease (AAD). This reduction in inflammation was accompanied by a significant decrease in airway hyper-responsiveness. SDF-1alpha neutralization resulted in similar reduction in both lung allergic inflammation and airway hyper-responsiveness. Retroviral delivery of a CXCR4 cDNA to leukocytes resulted in greater inflammation when transduced mice were subjected to a mouse model of AAD. These results highlight that, although considered a noninflammatory axis, the involvement of CXCR4 and SDF-1alpha is critical during AAD, and this receptor and its ligand are potentially relevant in other inflammatory processes.     

肥胖诱发胰岛素抵抗的炎性机制

肥胖可诱发一系列慢性代谢性疾病,如2型糖尿病、血脂障碍、高血压和非酒精性脂肪肝等.这些疾病构成了当今世界人类健康的极大威胁.胰岛素抵抗是这些疾病的共有特征.胰岛素抵抗的发生与慢性低度系统炎性密切相关,涉及多条炎性信号通路的激活和胰岛素信号转导的缺陷.本文综述了肥胖、炎性与胰岛素抵抗之间的本质联系,以及肥胖诱发胰岛素抵抗的炎性机制,以期为肥胖相关疾病的防治提供重要参考.     

House Dust Mite Induced Lung Inflammation Does Not Alter Circulating Vitamin D Levels

Low circulating levels of 25-hydroxyvitamin D [25(OH)D] are associated with chronic lung diseases such as asthma. However, it is unclear whether vitamin D is involved in disease pathogenesis or is modified by the inflammation associated with the disease process. We hypothesized that allergic inflammation decreases the level of circulating 25(OH)D and tested this using a mice model of house dust mite (HDM) induced allergic airway inflammation. Cellular influx was measured in bronchoalvelar lavage (BAL) fluid, and allergic sensitization and 25(OH)D levels were measured in serum. Exposure to HDM caused a robust inflammatory response in the lung that was enhanced by prior influenza infection. These responses were not associated with any change in circulating levels of 25(OH)D. These data suggest that alterations in circulating 25(OH)D levels induced by Th-2 driven inflammation are unlikely to explain the cross-sectional epidemiological association between vitamin D deficiency and asthma.     

A trial of the use of mupirocin in the nasal carriage of Staphylococcus aureus in medical personnel]

Many hospital-acquired purulent diseases and wound infections are due to multiresistant hospital strains of Staphylococcus aureus. The role of S. aureus nasal carriage in development of wound infections due to autoinfection is confirmed. Not only inpatients but also hospital staff can be highly colonized with coagulase positive staphylococci. The S. aureus persistence in hospital personnel results in distribution of the microorganisms in the environment. Therefore, detection of S. aureus carriers without signs of the infection among the hospital personnel and eradication of the pathogen make it possible to control outbreaks of S. aureus infection in hospitals. Clinical efficacy of nasal ointment of mupirocin in the treatment of S. aureus carriers among the intensive care personnel of the N. N.Blokhin Cancer Research Center was evaluated. S. aureus nasal carriage was diagnosed in 17 (26 per cent) out of 65 persons. All the isolates were susceptible to oxacillin. 5-7 days after discontinuation of the mupirocin nasal ointment use eradication of S. aureus was stated in 100 per cent of the cases. The effect was still observed in 94 per cent of the cases in 1 month, in 76 per cent of the cases in 5-6 months and in 60 per cent of the cases in 8-9 months. It is believed that mupirocin nasal ointment (Bactroban) is convenient to use, low toxic and highly active in the treatment of persons with S. aureus nasal carriage.     

Clinical application of biological research

Salivary glands may be involved in a wide variety of diseases, which may be broadly grouped into (1) inflammatory, (2) noninflammatory, nonneoplastic and (3) neoplastic categories.Most inflammatory and noninflammatory, nonneoplastic diseases should be managed conservatively and symptomatically. The common exceptions are first-arch branchialcleft cysts and calculi.Neoplastic lesions always require resection if that is feasible. For benign tumors, simple excision with a cuff of normal tissue around it will usually suffice. The prevailing trend for treatment of malignant neoplasms is conservatism. No longer is the facial nerve routinely sacrificed. The resection done is dictated by the tumor size and the facial nerve is spared unless directly invaded. Postoperative radiation therapy is increasingly used.     

Comparative characteristics of the antibioticograms and biological properties of the staphylococci isolated from patients with various eye diseases]

A total of 1488 examinations of the conjunctival content of patients with various ophthalmic diseases were performed within 5 years (1973--1977). 989 (66.4 per cent) cultures were isolated. Staphylococci were isolated in 79.2 per cent of the patients irrespective of the diagnosis. The plasma-coagulating strains were isolated in 43.6 per cent of the patients with acute conjunctivitis. The plasma-negative staphylococci were more frequent in chronic conjunctivitis (83.5 per cent). A total of 188 strains were studied according to 18 tests. Determination of the antibiotic sensitivity showed that the number of the benzylpenicillin and tetracycline resistant strains among the plasma-coagulating staphylococci was higher in the patients with acute ophthalmic diseases. In chronic conjunctivitis no differences in the antibiotic sensitivity of the plasma-coagulating and plasma-negative strains were noted. Similar antibiotic sensitivity of all plasma-negative staphylococci irrespective of the diagnosis was found. High biological activity of the plasma-negative staphylococci was shown: 74.1 per cent of the isolates possessed phosphatase, 59.8 per cent possessed protease and 88.4 per cent a lysozyme-like enzyme. The strains isolated in chronic conjunctivitis produced protease more frequently that those isolated in acute ophthalmic diseases.