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Biomedical subjects

S S Shin

Publications and source records attributed to S S Shin.

At least 19 recordsLinked to original sources
PubMed2006

Anti-inflammatory effect of jeongshintang through suppression of p38 activation in human astrocytoma, U373MG cells.

Jeongshintang (JST) is a Korean herbal prescription, which has been successfully used for cerebral diseases. However, the anti-inflammatory effect of JST on Alzheimer's disease (AD) is still not fully understood. In this study, we investigated the effects of JST in attenuating the inflammatory response induced by interleukin (IL)-1beta plus beta-amyloid [1-42] fragment (A beta) in the human astrocyte cell line, U373MG. The production of IL-6, IL-8, and prostaglandin (PG)E2 was significantly increased by IL-1beta plus A beta (1-42) in a time-dependent manner (P < 0.05). JST significantly inhibited the IL-1beta plus A beta (1-42)-induced IL-6, IL-8, and PGE2 production at 24 h (P < 0.05). Maximal inhibition rate of IL-6, IL-8, and PGE2 production by JST was about 54.40%, 56.01%, and 44.06% respectively. JST (0.01-1 mg/ml) also attenuated the expression of cyclooxygenase (COX)-2 and activation of p38 MAPK induced by IL-1beta and A beta (1-42). These results demonstrated that JST has an anti-inflammatory effect, which might explain its beneficial effect in the treatment of various neurodegenerative diseases such as AD.

Amyloid beta-Peptides↗
PubMed2006

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

Adolescent↗
PubMed2006

Causes of death during tuberculosis treatment in Tomsk Oblast, Russia.

SETTING: Tuberculosis (TB) incidence and mortality in Russia have risen dramatically over the past 15 years. OBJECTIVE: To identify risk factors and causes of death among TB patients in Russia. DESIGN: A retrospective study conducted to determine the risk factors and causes of death in patients receiving TB therapy in Tomsk, Siberia. RESULTS: Of 1916 patients who initiated treatment between 1 January 2002 and 31 December 2003, 183 (9.6%) died during treatment, 38 (21%) in the first week of therapy. Twenty-five per cent of deaths were not directly attributable to TB. Risk factors for death included older age, previous treatment for TB, multidrug resistance and alcoholism. CONCLUSIONS: The high death rate during TB treatment observed in this cohort likely reflects an increased risk of dying not only from TB, but also from comorbid conditions, such as alcoholism and cardiovascular disease. Overall, alcoholism and late presentation both contributed substantially to the mortality in this cohort.

Adult↗
PubMed2005

Mesenteric inflammatory myofibroblastic tumor mimicking a necrotized malignant mass in an adult: case report with MR findings.

Inflammatory myofibroblastic tumors are lesions that usually affect young adults and children. Numerous extrapulmonary sites of these tumors have been found, but the mesentery is a very unusual location for an inflammatory myofibroblastic tumor and it is extremely rare in an older patient. Inflammatory myofibroblastic tumor of the mesentery is often demonstrated as a large and infiltrative lesion with heterogeneous enhancement. Its diagnosis is recognized as difficult and it often mimics malignant tumor. We report a case of mesenteric inflammatory myofibroblastic tumor mimicking a necrotized malignant mass in a 55-year-old man who was examined with magnetic resonance imaging. To our knowledge, this is the first report of magnetic resonance imaging of mesenteric inflammatory myofibroblastic tumor with extensive central necrosis in an older patient.

Diagnosis, Differential↗
PubMed2005

rpoB gene mutations in clinical isolates of multidrug-resistant Mycobacterium tuberculosis in northern Lima, Peru.

In many developing countries and outside hospital settings, the characteristics of endemic Mycobacterium tuberculosis strains resistant to multiple drugs remain unknown. In a community-based referral and therapy program in northern Lima, Peru, beginning in 1996, patients found to be failures on standard regimens were referred for drug-susceptibility testing of their isolates, and those found to be infected with M. tuberculosis isolates resistant to at least rifampin were treated with individualized regimens based on their infecting strains. Isolates from 42 of these patients were subjected to DNA sequencing of the rpoB gene region responsible for rifampin resistance. We determined the frequency of types of mutations in the rpoB gene among these Peruvian isolates.

Antibiotics, Antitubercular↗
PubMed2005

Validation of a rapid method for detection of M. tuberculosis resistance to isoniazid and rifampin in Lima, Peru.

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is often based on drug susceptibility testing (DST) results; for this reason, rapid, simple DST methods are sought which could be applied in resource-poor countries. One such method is a nitrate reductase colorimetric assay known as the Griess method. In Peru, where the incidence rate of TB is among the highest in South America, the National Institute of Health recently undertook the validation and implementation of the direct Griess method. OBJECTIVE: To describe the process of validation and implemention of the direct Griess method at the Peruvian National Institute of Health. DESIGN: Prospective study comparing the sensitivity and specificity of the direct Griess method with the Löwenstein-Jensen proportion method in determining resistance to isoniazid (INH) and rifampin (RMP) among clinical isolates. RESULTS: Among 192 specimens, the sensitivity and specificity of the Griess method for detection of INH resistance was 99.1% and 100%, respectively. For identification of RMP resistance, the sensitivity and specificity was 93.5% and 100%, respectively. CONCLUSIONS: In addition to its high sensitivity and specificity and rapid turn around time, the Griess method uses simple, inexpensive reagents and requires minimal laboratory space and technical expertise, thus providing an ideal screening tool for resource-poor settings with high rates of MDR-TB.

Colorimetry↗
PubMed2005

Acquisition of drug resistance in multidrug-resistant Mycobacterium tuberculosis during directly observed empiric retreatment with standardized regimens.

The risk of acquiring additional drug resistance in strains of multidrug-resistant tuberculosis (MDR-TB) during failure of empiric standardized retreatment regimens is poorly defined. We sought to estimate this risk by comparing drug susceptibility profiles and RFLP patterns of paired MDR-TB isolates collected from 27 patients before and after retreatment failure. Among 23 patients with paired isolates with concordant RFLP patterns, 19 (83%) had become resistant to at least one additional drug after failed retreatment. In this limited group of MDR-TB patients, acquisition of resistance was common during failure of empiric drug regimens. Further study is needed to confirm these findings.

Adolescent↗
PubMed2003

Suppressive effects of PG201, an ethanol extract from herbs, on collagen-induced arthritis in mice.

OBJECTIVE: PG201 has been formulated using 12 herbs known to have anti-inflammatory and protective effects on damaged tissue and bone among other functions. The present study was done in order to assess the therapeutic effects of PG201 in collagen-induced arthritis (CIA) in mice. METHODS: DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with PG201 orally at 10 mg/kg once a day for 18 days. Paws were evaluated macroscopically for redness, swelling and deformities. The levels of TNF-alpha and IL-1beta in the ankle were examined. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Molecular indicators related to CIA pathology were analysed by measuring the serum levels of matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. RESULTS: Administration of PG201 significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-1beta in the paws. The erosion of cartilage was dramatically reduced in mouse knees after treatment with PG201. In the serum of PG201-treated mice, the level of TIMP-2 and the ratio of TIMP-2 to MMP-2 were significantly elevated, and the level of IL-4, but not of IL-10, was increased. CONCLUSION: Administration of PG201 has therapeutic effects on CIA. Protection of cartilage was particularly prominent. PG201 is a potential therapy for rheumatoid arthritis.

Animals↗
PubMed2003

Peripheral neuropathy associated with treatment for multidrug-resistant tuberculosis.

OBJECTIVE: To review the incidence and management of peripheral neuropathy in patients receiving therapy for MDR-TB. METHODS: A case series with retrospective chart review of 75 patients who initiated individualized therapy for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru, between 1 August 1996 and 31 January 1999. RESULTS: All patients had confirmed MDR-TB and were receiving individualized therapy, comprised of an average of six drugs. Ten (13%) of these patients presented with symptoms of peripheral neuropathy, confirmed by electromyography. All symptoms were reported in the lower extremities, and all were sensory in nature. Median time to presentation from initiation of MDR-TB therapy was 9.1 months. No significant risk factors associated with development of peripheral neuropathy were identified. Management strategies depended on the severity of symptoms and included the treatment of contributing co-morbidities, medications for neuropathic pain, and adjustment of doses of possible offending agents. All patients responded to management; three patients were left with mild residual symptoms. Patients whose neuropathy resolved had symptoms for a median of 7 months. CONCLUSIONS: Peripheral neuropathy was encountered in 13% of our cohort of MDR-TB patients. The diagnosis of peripheral neuropathy can be based on clinical presentation alone, and effective management of this side-effect is possible without sacrificing MDR-TB treatment efficacy.

Adolescent↗
PubMed2003

Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru.

SETTING: Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB. OBJECTIVE: To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs. RESULTS: Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy. CONCLUSIONS: Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

Adolescent↗
PubMed2001

Trends in immunologic and clinical status of newly diagnosed HIV-positive patients initiating care in the HAART era.

OBJECTIVE: To evaluate whether the availability of highly active antiretroviral therapy (HAART) has motivated people at risk for HIV infection to be tested earlier. METHODS: Data are from the Adult and Adolescent Spectrum of HIV Disease (ASD) Study, a chart review study of HIV-infected people receiving care. The sample comprised newly diagnosed HIV-positive persons initiating care at five ASD clinics in New York City (NYC) 1994 to 1999. CD4 + lymphocyte count and clinical status (asymptomatic, major AIDS-related symptoms, AIDS-defining opportunistic illnesses) at first visit were ascertained. Trends in these two outcomes were analyzed comparing each time period after the second half of 1996 with the aggregate period from 1994 to the first half of 1996. RESULTS: Between 1994 and 1999, we identified 545 patients newly diagnosed as positive for HIV with a first visit to an ASD clinic. Patients were predominantly black or Hispanic (93%). The mean CD4 + count at baseline was 246 cells/microl and the median was 152 cells/microl. After adjusting for covariates, the mean CD4 + count of newly diagnosed HIV-positive patients was significantly lower ( p =.04) only during the second half of 1997. The proportion of patients who were asymptomatic at baseline ranged from 29% in the second half of 1998 to 61% in the first half of 1994 (chi 2 = 48.8; p =.0008). After adjustment for covariates, the probability of a patient having a major symptom or an opportunistic illness at baseline was significantly higher only during the second half of 1998 ( p =.001). DISCUSSION: During most time periods, both before and after the introduction of HAART, most newly diagnosed patients at these five HIV clinics in NYC were immune suppressed and symptomatic.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design.

In our continuation of the structure-based design of anti-trypanosomatid drugs, parasite-selective adenosine analogues were identified as low micromolar inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Crystal structures of Trypanosoma brucei, Trypanosoma cruzi, Leishmania mexicana, and human GAPDH's provided details of how the adenosyl moiety of NAD(+) interacts with the proteins, and this facilitated the understanding of the relative affinities of a series of adenosine analogues for the various GAPDH's. From exploration of modifications of the naphthalenemethyl and benzamide substituents of a lead compound, N(6)-(1-naphthalenemethyl)-2'-deoxy-2'-(3-methoxybenzamido)adenosine (6e), N(6)-(substituted-naphthalenemethyl)-2'-deoxy-2'-(substituted-benzamido)adenosine analogues were investigated. N(6)-(1-Naphthalenemethyl)-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (6m), N(6)-[1-(3-hydroxynaphthalene)methyl]-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (7m), N(6)-[1-(3-methoxynaphthalene)methyl]-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (9m), N(6)-(2-naphthalenemethyl)-2'-deoxy-2'-(3-methoxybenzamido)adenosine (11e), and N(6)-(2-naphthalenemethyl)-2'-deoxy-2'-(3,5-dimethoxybenzamido)adenosine (11m) demonstrated a 2- to 3-fold improvement over 6e and a 7100- to 25000-fold improvement over the adenosine template. IC(50)'s of these compounds were in the range 2-12 microM for T. brucei, T. cruzi, and L. mexicana GAPDH's, and these compounds did not inhibit mammalian GAPDH when tested at their solubility limit. To explore more thoroughly the structure-activity relationships of this class of compounds, a library of 240 N(6)-(substituted)-2'-deoxy-2'-(amido)adenosine analogues was generated using parallel solution-phase synthesis with N(6) and C2' substituents chosen on the basis of computational docking scores. This resulted in the identification of 40 additional compounds that inhibit parasite GAPDH's in the low micromolar range. We also explored adenosine analogues containing 5'-amido substituents and found that 2',5'-dideoxy-2'-(3,5-dimethoxybenzamido)-5'-(diphenylacetamido)adenosine (49) displays an IC(50) of 60-100 microM against the three parasite GAPDH's.

3T3 Cells↗
PubMed2001

High glucose levels alter angiotensin II-induced Ca(2+) uptake via PKC and cAMP pathways in renal proximal tubular cells.

Although a dysfunction of the calcium metabolism occurs in diabetes mellitus, alterations of Ca(2+) uptake induced by angiotensin II (ANG II) in renal proximal tubular cells (PTCs) grown in high-glucose medium are not fully elucidated. Thus, we examined whether high glucose concentrations can induce an alteration of the ANG II effect on the Ca(2+) uptake and its action mechanism in primary cultured renal PTCs. PTCs were exposed to different glucose concentrations (5-100 mM) and time intervals (0-48 h). There was a sustained increase of Ca(2+) uptake at glucose concentrations >15 mM. Thus, we selected 25 mM glucose and incubation for 48 h to maintain a hyperglycemic condition in vitro, unlike short-time regulatin. ANG II significantly inhibited the Ca(2+) uptake in a dose-dependent manner in a 5-mM glucose medium. In addition, downregulation of ANG II receptors appeared in a glucose dose dependent manner. However, PTCs treated with 25 mM glucose for 48 h, not 12 h, did not exhibit the inhibitory effect of ANG II (10(-7) M) on Ca(2+) uptake, although the inhibitory effect of ANG II on Ca(2+) uptake occurred in the presence of 25 mM mannitol or L-glucose. Staurosporine, bisindolylmaleimide I (protein kinase C, PKC, inhibitors), 12-o-tetradecanoylphorbol 13-acetate pretreatment, SQ 22536 (an adenylate cyclase inhibitor), and myristoylated protein kinase A inhibitor amide 14-22 (a protein kinase A inhibitor) blocked the 25-mM-glucose-induced alteration of ANG II effect on Ca(2+) uptake. These results suggest that both PKC and cyclic adenosine monophosphate (cAMP) pathways are involved in the high-glucose-induced alteration of ANG II effect on Ca(2+) uptake. Indeed, 25 mM glucose increased PKC activity and cAMP contents. In conclusion, a high glucose concentration altered ANG II induced inhibition of Ca(2+) uptake via PKC and cAMP pathways in the PTCs.

Angiotensin II↗
PubMed2001

Experimental induction of the two-host life cycle of Sarcocystis cruzi between dogs and Korean native calves.

Eight dogs were experimentally infected with Sarcocystis by oral inoculation of cardiac muscle from naturally infected cattle. The infected dogs commenced discharging of sporocysts in the feces after 10 to 12 days of inoculation, and continued until 20 and 35 days after inoculation. Three dogs were reinfected with cardiac muscle from the naturally infected cattle. Sporocysts reappeared in the feces on 12 to 13 days after reinfection. Sarcocystis sporocysts collected from the experimentally infected dogs were fed to each of the two 30-day-old Korean native calves. The infected calves remained clinically normal, except for the high fever (> or = 40 degrees C) and decreased hematocrit values on day 30 to 40 post inoculation. Muscular cysts of Sarcocystis were found from infected calves on day 40 post inoculation. Proliferative forms of Sarcocystis were also observed in the muscle of infected calves. These results suggest that the Sarcocystis cruzi found in Korean native cattle has a 2-host life cycle with dogs as the definitive host and Korean native calves as the intermediate host.

Animals↗
PubMed2001

Peroral immunization with Helicobacter pylori adhesin protein genetically linked to cholera toxin A2B subunits.

Helicobacter pylori is a major cause of gastric-associated diseases. To evaluate the efficacy of a possible vaccine antigen against H. pylori infection, the chimaeric construct adhesin--CTXA2B, derived from H. pylori adhesin genetically coupled to cholera toxin (CTX) subunits A2 and B (CTXA2B), was expressed in Escherichia coli as an insoluble recombinant chimaeric protein. The protein was then purified by denaturation, renaturation and size-exclusion chromatography. The composition of purified adhesin--CTXA2B was verified by SDS/PAGE and Western blotting with antibodies to antigenic components of adhesin and CTXB, and confirmed as a chimaeric protein with G(M1)-ganglioside binding activity and adhesin epitopes by a G(M1)-ELISA developed using antibodies to adhesin. Oral immunization of mice with adhesin--CTXA2B induced higher levels of mucosal IgA and serum IgG antibodies to H. pylori adhesin and to CTXB than in mice immunized with adhesin or CTXA2B alone. Adhesin--CTXA2B was also demonstrated to be a potential protective antigen in a mouse model of H. pylori infection. The immunization of mice with adhesin--CTXA2B protected 62.5% of mice infected with H. pylori SS1 strain, whereas adhesin immunization was not able to confer protection to mice. This protection may be correlated with high levels of mucosal IgA and serum IgG antibodies against H. pylori adhesin. Taken together, the results indicate that the genetically linked CTXA2B acts as a useful mucosal adjuvant, and that the adhesin-CTXA2B chimaeric protein could be a potential component in future H. pylori vaccine development.

Adhesins, Bacterial↗
PubMed2001

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Adolescent↗
PubMed2000

Trends in prescriptions for highly active antiretroviral therapy in four New York City HIV clinics.

OBJECTIVE: To describe trends in prescriptions for antiretroviral therapies and factors associated with prescriptions for highly active antiretroviral therapy (HAART). METHODS: Medical records of patients at four HIV clinics in New York City were reviewed every 6 months. For the four 6-month periods 1997 to 1998, we identified patients with a CD4+ nadir <500 cells/microl; sample sizes were 434, 432, 503, and 643, respectively. Trends in HAART prescriptions were tested by logistic regression using robust variance estimates because some patients contributed more than one time period. Associations between HAART prescriptions and patient characteristics were tested by chi2 and multiple logistic regression analysis. RESULTS: Patients were predominantly black or Hispanic (89%-90%) and male (66%-68%), and injection drug use was the most prevalent HIV risk (38%-49%). From 1997 to 1998, HAART prescriptions increased from 54% to 89% of antiretroviral prescriptions, and the proportion that included an nonnucleoside reverse transcriptase inhibitors (NNRTI) increased from 3% to 10%. HAART prescriptions were inversely associated with CD4+ nadir group during all time periods, and in the second half of 1998, patients with CD4+ nadir between 50 and 199 cells/microl were as likely to be prescribed HAART as the most immunosuppressed patients (CD4+ nadir <50 cells/microl; 91% versus 92%). HAART prescriptions were associated with clinic, HIV risk, and other patient characteristics in some time periods but not consistently. CONCLUSIONS: In these four HIV clinics, prescriptions for HAART increased significantly from 1997 to 1998, leveling off at 89% in the second half of 1998. Increasingly, HAART was prescribed for healthier patients and included an NNRTI.

Adult↗