Search PubMed⌕ Search

Biomedical subjects

R Agarwal

Publications and source records attributed to R Agarwal.

At least 109 records · Page 6Linked to original sources
PubMed2000

Studies of ion-exchange resin complex of chloroquine phosphate.

High-potency adsorbates of chloroquine phosphate (CQP) were prepared by the batch method using a polyacrylic acid ion-exchange resin. Taste evaluation of the adsorbates shows significant masking of the bitterness of the drug. The complex formation was complete at pH 6.0. Stability studies at 37 degrees C, 45 degrees C, and 60 degrees C indicated that the complex was stable at all conditions for 1 month. In vitro release studies revealed complete drug elution from the complex at pH 1.2 and 2.0.

Acrylic Resins↗
PubMed2000

Impairment of erbB1 receptor and fluid-phase endocytosis and associated mitogenic signaling by inositol hexaphosphate in human prostate carcinoma DU145 cells.

Recently, we observed that epidermal growth factor receptor (EGFR or erbB1) endocytosis and associated mitogenic signaling occur in human prostate cancer (PCA) cells, suggesting that erbB1 endocytosis might be involved in advanced and androgen-independent PCA growth. Based on these findings, and the fact that aberrant expression of erbB family members is common in human prostatic intraepithelial neoplasia and invasive PCA, we reasoned that impairment of erbB1 endocytosis and associated mitogenic signaling might inhibit PCA growth. Inositol hexaphosphate (IP6) interacts with plasma membrane clathrin-associated protein complex 2 (AP2) and inhibits phosphatidylinositol 3-kinase (PI3K). As these are essential components of receptor-mediated and fluid-phase endocytosis, respectively, we reasoned that IP6 might impair erbB1 endocytosis and associated signaling in human PCA cells, leading to their growth inhibition. IP6 strongly to completely inhibited (26-100%; P < 0.05) transforming growth factor alpha-induced binding of activated erbB1 to AP2 in human PCA DU145 cells, demonstrating the impairment of the initial step in ligand-induced erbB1 endocytosis. IP6 treatment of cells resulted in a dose-dependent increase (1.8- to 7. 7-fold compared with cells treated with ligand alone; P < 0.05) in levels of activated erbB1. These two findings suggest that the inhibitory effect of IP6 on receptor endocytosis is independent of its lack of effect on ligand-induced erbB1 activation. These effects of IP6, however, were associated with strong inhibition of ligand-induced Shc phosphorylation (77-84% decrease; P < 0.05) and its binding to erbB1 (58-100% decrease; P < 0.05). IP6 also significantly and dose-dependently inhibited fluid-phase endocytosis (19-52%; P < 0.05). It inhibited PI3K-AKT signaling pathway as an upstream response in its effect on the inhibition of fluid-phase endocytosis. The inhibition of erbB1 receptor and fluid-phase endocytosis, and associated signaling by IP6, was corroborated by very strong to complete inhibition (70-100%; P < 0.05) of extracellular signal-regulated protein kinase 1/2 activation by IP6. IP6 significantly (P < 0.05) inhibited anchorage-dependent and -independent inhibition (50-100% and 30-75%, respectively) in DU145 cells. Targeting the impairment of erbB1 endocytosis and associated mitogenic signaling by IP6 in advanced and androgen-independent human PCA DU145 cells could be a useful approach for treating PCA.

Adaptor Protein Complex 2↗
PubMed2000

Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin.

In this communication, we investigate the preventive effect of a flavonoid antioxidant, silymarin, on free radical-generating skin tumor promoting agent benzoyl peroxide (BPO)-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Topical application of silymarin at a dose of 6 mg prior to BPO resulted in a highly significant protection against BPO-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin. The preventive effect of silymarin was evident in terms of a 70% reduction (P < 0.001) in tumor incidence, a 67% reduction (P < 0.001) in tumor multiplicity and a 44% decrease (P < 0.001) in tumor volume/tumor. In oxidative stress studies, topical application of BPO resulted in 75, 87 and 61% depletion in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities in mouse epidermis, respectively. These decreases in antioxidant enzyme activities were significantly (P < 0.005-0.001) reversed by pre-application of silymarin in a dose-dependent manner. The observed effects of silymarin were 18-66, 32-72 and 20-67% protection against BPO-induced depletion of SOD, catalase and GPX activity in mouse epidermis, respectively. Silymarin pre-treatment also resulted in a dose-dependent inhibition (35-87%, P < 0.05-0. 001) of BPO-induced lipid peroxidation in mouse epidermis. In inflammatory response studies, silymarin showed a strong inhibition of BPO-induced skin edema (62-85% inhibition, P < 0.001), myeloperoxidase activity (42-100% inhibition, P < 0.001) and interleukin-1alpha protein level in epidermis (36-81% inhibition, P < 0.001). These results, together with our other recent studies, suggest that silymarin could be useful in preventing a wide range of carcinogen and tumor promoter-induced cancers.

Animals↗
PubMed2000

ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group.

BACKGROUND: Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency. METHODS: The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. RESULTS: For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). CONCLUSIONS: In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

Aldosterone↗
PubMed2000

Role of interleukin-12 in patients with dengue hemorrhagic fever.

Interleukin (IL)-12 has a broad range of activities including regulation of cytokine synthesis and selective promotion of Th1-type cell development. A shift from a Th1-type response to Th2-type has been suggested to be important in the pathogenesis of dengue hemorrhagic fever (DHF). This study was undertaken to investigate the possible role of IL-12 in this shift. A total of 76 patients with various grades of dengue illness and 21 normal healthy controls were tested for IL-12 levels in serum samples and IL-12 mRNA in their peripheral blood mononuclear cells. The results showed that the levels of IL-12 were the highest in patients with dengue fever (270+/-102 pg ml(-1)) followed by decreasing levels in the patients with DHF grade I (198+/-86 pg ml(-1); P<0.05) and DHF grade II (84+/-52 pg ml(-1); P<0.001). Neither IL-12 nor its mRNA could be detected in the patients with DHF grades III and IV. The cytokine appeared and reached peak levels during the first 4 days of illness, started to decline by day 5-8 and disappeared by day 9 onwards. The absence of IL-12 during severe illness and late phases of the disease may be responsible for the shift to a Th2-type response and thus for the pathogenesis of DHF.

Enzyme-Linked Immunosorbent Assay↗
PubMed2000

Cytokine cascade in dengue hemorrhagic fever: implications for pathogenesis.

Dengue virus produces a mild acute febrile illness, dengue fever (DF) and a severe illness, dengue hemorrhagic fever (DHF). The characteristic feature of DHF is increased capillary permeability leading to extensive plasma leakage in serous cavities resulting in shock. The pathogenesis of DHF is not fully understood. This paper presents a cascade of cytokines, that in our view, may lead to DHF. The main feature is the early generation of a unique cytokine, human cytotoxic factor (hCF) that initiates a series of events leading to a shift from Th1-type response in mild illness to a Th2-type response resulting in severe DHF. The shift from Th1 to Th2 is regulated by the relative levels of interferon-gamma and interleukin (IL)-10 and between IL-12 and transforming growth factor-beta, which showed an inverse relationship in patients with DF.

Animals↗
PubMed2000

Clinico-histopathological concordance in leprosy.

Histopathological examination of biopsies from 111 patients with clinically diagnosed leprosy was carried out in order to observe the clinico-histopathological correlation. Clinical diagnosis was based on Ridley and Jopling (R-J) classification and World Health Organization (WHO) classification. The concordance rate between the two clinical classifications was 73.8%. Sections were stained with haematoxylin and eosin (H&E) and Ziehl-Neelsen's (Z-N) stains. The histological classification was as per the R-J criteria. Skin biopsy showed evidence of leprosy in 104 cases (93.69%). Overall concordance was observed in 58.6% (R-J) and 85.6% (WHO classification). The kappa test, when applied, showed significant agreement between clinical and histopathological diagnosis (z=11.775; P<0.001). Individual subtypes showed variable concordance rates which were again higher using WHO classification. When some of the subtypes were combined, the concordance rate was 83.02% for TT+BT; 72.58% for BT+BB+BL; 73.91% for BL+LL; 80.77% for BL+HL and 100% for LL+HL. (See Introduction for definitions of abbreviations.) The present study highlights the importance of histopathological examination for exact subtyping of leprosy, so as to facilitate the institution of accurate mode of therapy and regular follow-up of patients to prevent undesirable complications.

Biopsy↗
PubMed2000

Otitic hydrocephalus of tubercular origin: a rare cause.

Otitic hydrocephalus is characterized by increased intra-cranial pressure without focal signs of neurological dysfunction. It usually occurs secondary to lateral sinus thrombosis more commonly on the right side, but it can also occur without lateral sinus thrombosis. With the advent of new antibiotics there has been a spectacular decrease in the complications of otitis media. Otogenic intra-cranial hypertension, always an uncommon condition, is seen only very rarely nowadays. Tubercular otitis media still occurs in India, and due to delays in its diagnosis it usually presents with complications. We present three patients with otitic hydrocephalus of tubercular origin.

Adolescent↗
PubMed2000

Lemierre's syndrome: a complication of acute oropharyngitis.

Lemierre's syndrome is a recognized but infrequently seen complication of acute oropharyngitis. In this case report the patient presented with acute sore throat that led to a bacteraemia with internal jugular vein thrombosis and subsequent cranial nerve palsies.

Accessory Nerve Diseases↗
PubMed2000

The pilosebaceous unit: a pivotal route for topical drug delivery.

The hair follicle, hair shaft and sebaceous gland are collectively known as the pilosebaceous unit. The pilosebaceous unit is a complex, dynamic, 3-D structure, which is the site of unique biochemical, metabolical and immunological events. Ongoing research has focused on the hair follicle as a potential route for both localized and systemic drug delivery. Targeted drug delivery to the specific sites of hair follicle has paved ways to treat several dermatological abnormalities that are known to originate at the hair follicle. In recent studies, topical liposomes have been shown to target the drug to the pilosebaceous unit. This review describes general aspects of pilosebaceous unit, follicular delivery, with particular emphasis on studies which have demonstrated targeted follicular delivery via liposomes.

Administration, Topical↗
PubMed2000

Effect of T-helper 1 cytokines on secretion of T-helper 2 cytokines by term trophoblast cells in culture.

A successful pregnancy has been postulated to be the result of a discrete balance between T-helper 1 (Th1) and T-helper 2 (Th2) type cytokines involved in growth and development of the conceptus. The aim of the present study was to examine the effect of Th1 cytokines (interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha)) on the release of Th2 cytokines including IL-6 and IL-10 by trophoblast cells obtained from term placenta. Trophoblast cells isolated by enzymatic disaggregation and Percoll gradient fractionation were cultured in supplemented medium alone or with varying concentrations of the selected recombinant cytokines. After 48 h of incubation, samples of the culture supernatant were analyzed for the Th2 cytokines IL-6 and IL-10 using specific ELISA assays. Both IL-1 beta and TNF alpha had no effect on the cell number and viability as determined by MTT assay. IL-1 beta significantly stimulated trophoblast release of IL-6 in a dose-dependent manner (3.3-, 5.5-, 10.3- and 22.4-fold higher compared to the control at 10, 50, 100, 500 U IL-1 beta/ml respectively, p < 0.05). TNF alpha also stimulated release of IL-6 by these cells. However, the stimulation at lower concentrations was not very high and a significant (p < 0.05) stimulation was observed only at higher concentrations (1.1-, 1.3-, 2.6- and 5.9-fold higher at 500, 1000, 1500, 2000 U TNF alpha/ml respectively). In contrast, neither IL-1 beta or TNF alpha exerted any significant effect on IL-10 release by term trophoblast cells (p > 0.05). The results of this study provide evidence that production of Th2 cytokines might be under the control of different regulatory pathways.

Cells, Cultured↗
PubMed2000

A polyphenolic fraction from grape seeds causes irreversible growth inhibition of breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases activation and inducing G1 arrest and differentiation.

In recent years, significant emphasis is being placed on identifying naturally occurring cancer preventive and interventive agents. In this regard, a polyphenolic fraction isolated from grape seeds (hereafter referred as GSP) has recently been shown by us and others to prevent tumorigenesis in mouse skin models. Chemical analysis of GSP has shown that it is largely constituted with procyanidins that are strong antioxidants. Breast cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths in United States women. Accordingly, here we investigated the effect of GSP on mitogenic signaling and regulators of cell cycle and apoptosis as molecular targets for the growth arrest, apoptotic death, and/or differentiation of estrogen-independent MDA-MB468 human breast carcinoma cells. Treatment of cells with GSP (at 25-, 50-, and 75-microg/ml doses for 1-3 days) resulted in a highly significant inhibition (90% to complete, P < 0.001) of constitutive activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein kinase1/2 in a dose-dependent manner after 72 h of treatment. Whereas GSP treatment of cells did not show a conclusive effect on MAPK/ JNK1 activation, a moderate to highly significant inhibition (15-70%, P < 0.1-0.001) of constitutive activation of MAPK/p38 was also observed in a dose-dependent manner as early as 24 h of GSP treatment. GSP-treated cells also showed a strong induction (1.7-2.7 fold, P < 0.001) of cyclin-dependent kinase inhibitor Cip1/p21 and a decrease (10-50%, P < 0.1-0.001) in cyclin-dependent kinase 4. Consistent with these findings, GSP-treated cells resulted in their accumulation in G1 phase of the cell cycle in a dose-dependent manner. An irreversible growth inhibition (44-88%, P < 0.001) was also observed in 50 and 75 microg/ml GSP-treated cells in a time-dependent manner. Additional studies assessing the biological fate of GSP-treated cells showed that they do not undergo apoptotic death, as evidenced by a lack of DNA fragmentation, poly (ADP ribose) polymerase cleavage, and apoptotic morphology of the cells. A morphological change suggestive of differentiation was observed in GSP-treated cells that was further confirmed by a significant induction (1.7-2.6 fold, P < 0.001), in both a dose- and time-dependent manner, in cytokeratin 8 protein level, a marker of differentiation. An irreversible growth-inhibitory effect of GSP possibly via terminal differentiation of human breast carcinoma cells suggests that GSP and the procyanidins present therein should be studied more extensively to be developed as preventive and/or interventive agents against breast cancer in humans.

Animals↗
PubMed2000

A trial of two iron-dextran infusion regimens in chronic hemodialysis patients.

AIM: To test the ability to elicit a hemoglobin (Hb) response in patients on chronic hemodialysis, we prospectively compared two regimens of iron dextran administration, 100 mg once weekly (QW) or 100 mg once every dialysis (QD), both given for 10 doses. PATIENTS AND METHODS: Twenty-three consecutive patients on chronic hemodialysis received iron dextran intravenously if they had absolute or functional iron deficiency. There was no difference in the Hb response between regimens. RESULTS: Both groups had a significant increase in Hb from 10.5+/-1.5 g/dl at baseline, to 11.1+/-1.7 g/dl at 1 month, 1.4+/-2.1 g/dl at 2 months and 11.6+/-1.9 g/dl at 3 months. The increment in Hb at 1 month was similar (QD 0.62+/-1.245 g/dl vs. QW 0.64+/-1.464 g/dl) between the two groups despite a large difference in the amount of iron received. Serum ferritin, transferrin saturations or epoetin dose did not change significantly. At the end of 3 months 12 patients did not need further iron therapy as judged by the serological markers of iron stores. Of these 12 patients, 3 had serum ferritins of > 1,000 ng/ml. Weekly dosing of iron was associated with more medication errors than dosing every dialysis. Baseline iron stores could not predict the responsiveness to intravenous iron therapy as judged by an increase in Hb concentration at 1 month or at 3 months. CONCLUSION: This study confirms the efficacy of 1,000 mg of intravenous iron administered over a 3-month period in patients with functional iron deficiency. It underscores the importance of careful monitoring of iron stores and highlights the need for developing better parameters of functional iron stores in hemodialysis patients.

Anemia, Iron-Deficiency↗
PubMed2000

Human trabecular meshwork cells secrete neurotrophins and express neurotrophin receptors (Trk).

PURPOSE: The purpose of this study was to compare the mRNA expression of neurotrophins (NTs) and NT receptors (Trk) in cultured human trabecular meshwork (HTM) cells and ex vivo HTM tissues, to immunolocalize both NT and Trk receptors in cultured HTM cells, and to demonstrate secretion of NTs by HTM cells. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of NT and Trk receptor mRNAs in early-passaged, cultured HTM cells from donors of several ages. RT-PCR was used on ex vivo HTM tissues from donors to compare and contrast mRNA expression with cell culture results. In addition, immunohistochemistry was used to localize the translated NT and low- (p75) and high- (Trk) affinity NT receptor proteins within cultured HTM cells and trabecular meshwork tissues. Last, enzyme-linked immunoassay (ELISA) was used to demonstrate secretion of NTs by HTM cells. RESULTS: Amplification products of the expected size for NTs were detected in both cultured HTM cells and ex vivo HTM tissues. Specifically identified were amplification products for the following NTs: NGF, BDNF, NT-3, and NT-4. Amplification products for the full-length Trk A and Trk C high-affinity receptor were observed, as well as truncated isoforms for Trk B and Trk C. No amplification products were produced for the full-length Trk B receptor nor for the low-affinity p75 receptor. Immunohistochemistry indicated that proteins for the various NTs and full-length and truncated Trk receptors were translated by cultured HTM cells and tissues. Immunoassays (ELISA) detected BDNF, NT-4, NGF, and NT-3 in the culture media from HTM cells. CONCLUSIONS: The results demonstrate, for the first time, mRNA expression for NT and Trk receptors by both cultured HTM cells and ex vivo HTM tissues. NTs were immunolocalized in HTM tissues and cultured HTM cells are capable of secreting NTs. Specific NTs acting through high-affinity Trk receptors within the HTM may be involved in maintaining the normal function of this complex tissue.

Adolescent↗
PubMed2000

Fine needle aspiration of bone tumors.

Fine needle aspiration cytology (FNAC) was performed in 226 cases of bone tumors and the cytohistologic correlation was calculated to assess the technique's diagnostic efficacy aided by immunocytochemistry, considering histopathology as the gold standard. Of the 226 cases, 136 were malignant and 72 cases were benign tumors. In the remaining 18 cases, cytohistopathologic examination revealed no bony lesion. There were 178 evaluable cases, but the specific morphologic diagnosis on FNAC was possible only in 159 cases with one false positive and 29 false negatives. Giant cell tumor (32%) and Ewing's sarcoma (22%) were the most common bony tumors encountered in this series. The diagnostic indices were calculated by a decision matrix comparison. The overall sensitivity and specificity were 86.0 (confidence interval [CI], 80.3-90.3) and 94.7 (CI, 71.9-99.7), respectively. The positive predictive value (PPV) was as high as 99.4 (CI, 96.5-100), while the negative predictive value (NPV) was 38.3 (CI, 24.9-53.6) with positive and negative likelihood ratios of 16.338 and 0.147, respectively. Diagnosis of malignant tumors was more accurate with a PPV of 99.2 (CI, 94.8-100.0) and specificity of 94.7 (CI, 71.9-99.7), while the sensitivity was 89.0 (CI, 82.2-93.5) and NPV was 54.5 (CI, 36.6-71.5). This study highlights the usefulness of FNAC along with the use of immunocytochemistry in the rapid diagnosis of bone tumors.

Adolescent↗
PubMed2000

Strategies and feasibility of hypertension control in a prevalent hemodialysis cohort.

BACKGROUND: There are few data to demonstrate the feasibility of long-term blood pressure (BP) control using short dialysis sessions as practiced in the US. Control of hypertension in hemodialysis patients may reduce the risk of cardiovascular events. METHODS: Forty-two dialysis patients had BPs and weights recorded before and after dialysis for two consecutive weeks and were followed by one physician over three years. Patients were treated by ultrafiltration and conventional antihypertensive drugs and BPs were repeated at three years in the 32 survivors. RESULTS: 93% of the patients (39/42) were African-American. At inception, 85% of the patients were hypertensive with BPs of 154 +/- 23/83 +/- 14 mmHg and 137 +/- 22/74 +/- 14 mmHg pre- and post-dialysis, respectively. The response to ultrafiltration was dependent upon gender, with women having a greater BP reduction compared to men. At three-year follow-up, the BP had dropped significantly in the survivors a mean of 9.4/6.7 mmHg. Pre- and post-dialysis weights, post dialysis BP and interdialytic weight-gain were unchanged. The BP reduction was achieved by an increase in the number of antihypertensive medications from 0.91 +/- 0.86 medications to 1.41 +/- 1.16. Improved BP control did not worsen the efficiency of dialysis (Kt/V). The use of beta-blockers doubled during the period of follow-up. Compared to the USRDS average cardiovascular death rate, the risk of cardiovascular deaths was improved 80% over three years. CONCLUSION: Long-term BP reduction can be achieved through the use of antihypertensive agents and volume control in a predominantly African-American hemodialysis population. This may impact cardiovascular mortality.

Adrenergic beta-Antagonists↗