Search

The usefulness of sirolimus (SIR) in the treatment of diseases that involve retinal degeneration like age-related macular degeneration (AMD) has been well documented. However, the problem still remains probably owing to the peculiar environment of the eye and/or unfavourable physiochemical profile of SIR. In the present work, we aimed to fabricate sirolimus loaded PLGA nanoparticles (SIR-PLGA-NP) and chitosan decorated PLGA nanoparticles (SIR-CH-PLGA-NP) to be administered via non-invasive subconjunctival route. Both the nanoparticles were characterized in terms of size, zeta potential, DSC, FTIR and XRD analysis. Quality by Design (QbD) approach was employed during the preparation of nanoparticles and the presence of chitosan coating was confirmed through thermogravimetric analysis and contact angle studies. Cationic polymer modification showed sustained in-vitro SIR release and enhanced ex-vivo scleral permeation and penetration. Further, SIR-CH-PLGA-NP revealed enhanced cellular uptake and thus, reduced lipopolysaccharide (LPS)-induced free-radicals generation by RAW 264.7 cells. The prepared nanoparticles were devoid of residual solvent and were found to be safe in HET-CAM analysis, RBCs damage analysis and histopathology studies. Moreover, high anti-angiogenic potential was observed in SIR-CH-PLGA-NP compared with SIR-PLGA-NP in chorioallantoic membrane (CAM) test. Overall, the current work opens up an avenue for further investigation of CH-PLGA-NP as SIR nanocarrier in the treatment of AMD.

Arsenic, a widespread environmental toxin, produces multiple organ toxicity, including hepatotoxicity. Thymoquinone (TQ) is known to restore liver functions in several hepatic injury models. This study aims to assess the mitigative potential of TQ against sodium arsenate (NaAs)-induced cytotoxic and genotoxic alterations in the liver. Rats were randomly distributed to control, NaAs, TQ, and NaAs+TQ groups. NaAs+TQ and TQ group of rats were pre-treated with TQ (1.5 mg/kg bwt, orally) for 14 days, and the treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. The deleterious histological alterations in the liver of arsenic intoxicated animals were accompanied by an upsurge in the activities of serum ALT and AST, the diagnostic indicators of liver injury. NaAs caused pronounced alterations in the activities of membrane marker and carbohydrate metabolic enzymes and the enzymatic and non-enzymatic components of hepatic antioxidant defense. Significant hepatocyte DNA damage and hepatic arsenic accumulation were also observed in arsenic-exposed rats. TQ supplementation alleviated these adverse alterations and improved the overall hepatic metabolic and antioxidant status in NaAs-administered rats. Prevention of oxidative injury could be the key mechanism of TQ-elicited protective effects. TQ may have an excellent scope as a dietary supplement in the management of arsenic-induced hepatic pathophysiology.

Background Arthritis is not an inherited disease but caused by stimulation of some hidden arthritis susceptible genes lowering the quality of life throughout the world, particularly in developing countries. Objectives To present a comprehensive review on ethnomedicinal and ethno-pharmacological information of Asian anti-arthritic plants. Data sources Research articles published in English were searched using six search engines (1979–2017). A few additional records searched from other sources i.e. floras, inventories and bibliographies were also included. Data Extraction Information regarding ethnobotany, pharmacology, phytochemistry and toxicity of plants used against arthritis was extracted from the selected literature. Results A total of 159 medicinal plants that were reported to be used against arthritis belonging to 71 families among which Asteraceae and Lamiaceae were dominant. Most of the plants were from India (37 plant species) followed by Thailand (21), China (16), and Iraq (12). Twelve percent of plants were reported to be traditionally used in more than one country. Most of the plants were used against rheumatoid arthritis (65). The majority of the documented herbal preparations consisted of leaves (22%) followed by roots (13%) and the dominant formulation method was decoction (21 plants). Only six plants were reportedly evaluated for their in-vitro and 15 plants for in-vivo activities. Five pure compounds (allicin, thymoquinone, polyphenols, 1′-acetoxychavicol acetate and ginger oil) were reportedly isolated from the documented plants and tested against different arthritis models. Toxicity of certain plants was also reported. Conclusion The present review summarizes the ethnomedicinal information of anti-arthritic plants and discloses scientific gaps in current knowledge. The majority of reported plants have not yet been scientifically authenticated and should be given more attention in future, especially those plants i.e. Carica papaya L. being used in more than one country.

Interaction of anionic bile salt sodium taurocholate (NaTaC) and anionic anti-inflammatory drug sodium salt of ibuprofen (NaIBU) in aqueous solutions together with in occurrence of 100 mmmol kg−1 NaCl and 250 mmmol kg−1 urea (NH2CONH2) using tensiometric and fluorometric techniques at 298.15 K temperature has been studied. A tensiometry study disclosed decreasing in surface tension (γ) along with critical micelle concentration (cmc) of NaIBU and NaTaC mixture, signifying a noteworthy interaction between studied components. Salt decreases the cmc of amphiphiles whereas urea increases their cmc in comparison to the aqueous solution. The solution mixture of NaIBU and NaTaC shows lower cmc value as compared to ideal cmc ( cmc id ) value indicating the non-ideality in the current studied systems. Other parameters regarding tensiometric technique such as micellar mole fraction of mixed micelles/mixed interface (X1m/X1σ), micellar/surface interaction parameter (βm/βσ), activity coefficients (f1m/f1σ and f2m/f2σ) of the mixed micelles/mixed interface, surface excess concentration ( Γ max ), excess Gibbs energy of mixed monolayer/mixed micelle formation ( Δ G ex σ / Δ G ex m ) etc. were estimated. The non-ideality of mixing expressed in terms of the interaction parameter (βm/βσ). Various thermodynamic parameters for current systems in all different media were obtained and discussed in detail. The aggregation number (Nagg), as well as other related parameters regarding fluorescence study, were also evaluated. The higher values of Nagg show the being of hydrophobic interactions along with sustains synergism.

Cisplatin (cis-diamminedichloroplatinum [II], CP) is most widely prescribed in chemotherapy and efficaciously treats diverse human cancers, with remission rates > 90% in testicular cancers. However, clinical use of CP is associated with numerous untoward side effects, in particular, at the gastrointestinal level that reduces the therapeutic efficacy of CP and often results in withdrawal of its clinical usage in long term cancer chemotherapy. Substantial strides have been made to identify effective protective strategies against CP-induced nephrotoxicity, hepatotoxicity and ototoxicity. Unfortunately, very limited studies have focused on CP-induced gastrointestinal toxicity and advances in developing potent gastroprotective strategies/agents are still lacking. The current article reviews the metabolism and pharmacokinetics of CP, mechanisms underlying CP-induced gastrointestinal toxicity and lastly displays the potential approaches including plant-derived agents (phytochemicals) utilized to counteract CP-induced gastrointestinal dysfunction. Furthermore, the gastroprotective agents described in the experimental literature have shown partial protection against CP-induced intestinal damage. This stresses the need to ascertain new information on the underlying mechanism and to discover novel combinatorial strategies for the abrogation of CP-induced gastrointestinal toxicity.

Highlights • Poor nutritional status and decreased lean body mass. • Decline in pulmonary function. • Increased mortality from lung disease. • Microvascular complications. • Macrovascular complications (not currently a significant complication but this may change with modulators)., Cystic fibrosis related diabetes (CFRD) occurs in at least 40–50% of adults with CF. With other forms of diabetes, microvascular and macrovascular disease are the major causes of morbidity and mortality. Macrovascular disease is rare in CF. While microvascular disease does occur in this population, there are CF-specific diabetes complications that have a more important impact on prognosis. The additional diagnosis of diabetes in CF is associated with decreased lung function, poor nutritional status, and an overall increase in mortality from lung disease. These negative findings start even before the clinical diagnosis of CFRD, during the period when patients experience abnormal glucose tolerance related to insulin insufficiency. The main mechanisms by which CFRD negatively affects prognosis are thought to be a combination of 1) protein catabolism, decreased lean body mass and undernutrition resulting from insulin insufficiency, and 2) an increased pro-inflammatory and pro-infectious state related to intermittent hyperglycemia. With the introduction of CFTR modulators, the care of CF patients has been revolutionized and many aspects of CF health such as BMI and lung function are improving. The impact of these drugs on the adverse prognosis related to the diagnosis of diabetes in CF, as well as the potential to delay or prevent onset of CFRD remain to be determined.

Ester bonded bio-cleavable gemini surfactant - ethane-1,2-diylbis(N,N-dimethyl-N-hexadecylammonium acetoxy)dichloride (16-E2-16) influences the micellization of promethazine hydrochloride (PMT) studied through surface tension, UV and FT-IR measurements in various media (aqueous, 50 mmol/kg sodium chloride (NaCl), 500 mmol/kg urea (U) and 500 mmol/kg thiourea (TU)) solutions. The solution and interfacial behavior show synergism between PMT and gemini surfactant in all the media. The addition of urea (U) and thiourea (TU) to the PMT, 16-E2-16, and PMT + 16-E2-16 mixture solution exhibit both increase and decrease in cmc hangs on concentration of [U] and [TU] and here the employed concentration of [U] or [TU] increases the cmc value of system while NaCl always decreases the cmc value. In mixed micelles, the micellar composition of 16-E2-16 is found higher than PMT. The micelle phase is found rich in surfactant monomers as compared to drug molecules. Activity coefficients in each case were attained below one in solution and interface, which authorized an interaction between constituents along with non-ideal behavior of mixtures. Different evaluated thermodynamic parameters depicted spontaneity as well as stability of mixed systems. UV–visible spectra showed that the absorption intensity of PMT increased with the addition of 16-E2-16 owing to interaction amongst them. FTIR investigation confirmed that the peak shifting in spectra of the pure component was detected also addressed the interaction amongst both components (PMT and 16-E2-16). Mixed micelles formation enhances solubility and permeability, so favorable for drug delivery purposes across the membrane.

In this study, aggregation, air/solvent interfacial surfaces and thermodynamic characteristics of the mixture of antidepressant drug imipramine hydrochloride (IMP) and ester-bonded gemini surfactant (ethane-1, 2-diyl bis(N,N-dimethyl-N-cetylammoniumacetoxy) dichloride (16-E2-16)) with different mole fractions (α1) of 16-E2-16 were explored through tensiometry technique at a temperature of 298.15 K. IMP is used to treat depression (antidepressant). The effect of several solvents (50 mmol·kg−1 NaCl, 500 mmol·kg−1 urea (U), and 500 mmol·kg−1 thiourea (TU)) other than the aqueous system on the interaction between IMP and 16-E2-16 were also explored. In aqueous system, the interactions between IMP and 16-E2-16 were estimated using UV–visible and FT-IR spectroscopy. Although the 16-E2-16 surfactant is biodegradable and IMP is used to treat depression, both ingredients are cationic. Tensiometric measurements that attained the critical micelle concentration (cmc) value of mixtures (IMP + 16-E2-16) were significantly less compared with the ideal cmc (cmcid) value. This confirmed a fair interaction between IMP and 16-E2-16 and that the interaction rises through a surge in α1 of 16-E2-16. In NaCl solvent, the attained cmc values of entire pure and mixed systems were less than with the aqueous system, whereas in U or TU solvent, the respective systems cmc values were more than with the aqueous system. U was found to be less effective than TU. Diverse parameters of aggregation and air/solvent interfacial and thermodynamic characteristics have been determined using Clint, Motomura, Rubingh, Rosen, etc. theoretical models. The activity coefficients parameter of micellar on air/solvent interfacial surfaces were regularly below 1 for each component, demonstrating the intermolecular interaction among components and non-ideal behavior of the mixed system. Akin to the tensiometric technique, UV–visible and FT-IR examination characterize the straightforward interaction between IMP and 16-E2-16. Overall, the obtained outcomes indicate an open method to design ester-bonded gemini surfactants to be proficient ingredients for the drug delivery vehicle.

Cisplatin (CP) is a widely used chemotherapeutic agent that elicits severe gastrointestinal toxicity. Nigella sativa, a member of family Ranunculaceae, is one of the most revered medicinal plant known for its numerous health benefits. Thymoquinone (TQ), a major bioactive component derived from the volatile oil of Nigella sativa seeds, has been shown to improve gastrointestinal functions in animal models of acute gastric/intestinal injury. In view of this, the aim of the present study was to investigate the protective effect of TQ on CP induced toxicity in rat intestine and to elucidate the mechanism underlying these effects. Rats were divided into four groups viz. control, CP, TQ and CP+TQ. Animals in CP+TQ and TQ groups were orally administered TQ (1.5mg/kg bwt) with and without a single intraperitoneal dose of CP (6mg/kg bwt) respectively. The effect of TQ was determined on CP induced alterations in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in rat intestine. TQ administration significantly mitigated CP induced decline in the specific activities of BBM marker enzymes, both in the mucosal homogenates and in the BBM vesicles (BBMV) prepared from intestinal mucosa. Furthermore, TQ administration restored the redox and metabolic status of intestinal mucosal tissue in CP treated rats. The biochemical results were supported by histopathological findings that showed extensive damage to intestine in CP treated rats and markedly preserved intestinal histoarchitecture in CP and TQ co-treated group. The biochemical and histological data suggest a protective effect of TQ against CP-induced gastrointestinal damage. Thus, TQ may have a potential for clinical application to counteract the accompanying gastrointestinal toxicity in CP chemotherapy.

Calcined Jade (CJ) is a metasilicate frequently used in traditional system of medicine as tonic to vital organs with several other pharmacological activities. X-ray powder diffraction (XRPD), inductively coupled plasma mass spectrometry (ICP-MS), atomic absorption spectroscopy (AAS) and CHNS analyzer techniques were used to characterize CJ sample. CJ was administered orally to Swiss albino mice at a dose of 50, 75, 100 and 200 μg/kg body weight for 10 days and modulation of the macrophage mediated innate immune responses was studied. Flow cytometric analysis of TLR-2/4 on peritoneal macrophage revealed elevated expression of TLR-2 as compared to control. Significant increase in phagocytic activity was observed in peritoneal macrophage. The lymphoid organs weight and other toxicity parameters did not exhibit any harmful effect. To evaluate the presence of nanoparticles, CJ was dissolved in milli Q water, filtered and lyophilized. Transmission electron microscopic (TEM) analysis revealed the presence of spherical nanoparticles in CJ [14.7–142.0 nm dimension with average particle size of 64.6 nm]. In conclusion, we report stimulation of innate immune responses by CJ may partly be due to the formation of nanoparticles. Further experiments using isolated nanoparticles may further validate the role of nanoparticles., Graphical abstract

SHP-1 (Src homology 2 domain containing protein tyrosine phosphatase) is a known negative regulator of insulin signaling and inflammation. To date, the molecular mechanism of metformin in modulating SHP-1 expression has remained elusive. In the present study, we have investigated the role of SHP-1 in relation to anti-hyperglycemic and anti-inflammatory actions of metformin in an obese phenotype mouse model. We observed that metformin treatment significantly reduced SHP-1 activity in obese mice, leading to improved insulin sensitivity. Additionally, metformin down regulated inflammatory markers like TLR2, TLR4, CD80, CD86, NF-κB, STAT1 and suppressed adipose tissue inflammation by efficiently polarizing adipose tissue macrophages toward anti-inflammatory state by way of indirect inhibition of SHP-1 mRNA and protein expressions. Our study suggests that metformin exerts its insulin sensitizing effects via inhibition of SHP-1 activity and expression.

The current study investigated the mixed micellization of a phenothiazine drug, promethazine hydrochloride (PMT), with the anionic hydrotrope sodium benzoate (NaB) using a conductometric method in three different solvent media: water, 50 mmol.kg−1 sodium chloride (NaCl), and 300 mmol.kg−1 urea (U). Five different temperatures, ranging from 293.15 to 313.15 K, were chosen for the current study of both pure and mixed systems. PMT belongs to a class of drugs known as antihistamines, which are used to treat allergy symptoms. Various physicochemical parameters of both pure and mixed systems (PMT+NaB) were evaluated at different compositions and temperatures, using numerous theoretical models associated with mixed micellization. The attained critical micelle concentration (cmc) and ideal cmc (cmcid) values indicated the formation of mixed micelles due to interactions between the components. The evaluated cmc value for PMT, the minimum hydrotropic concentration (mhc) of NaB, and the cmc value for the PMT+NaB mixture decreased in the NaCl system and increased in the U system compared with these values in the aqueous solution. The cmc values of the studied mixed systems decrease due to an upsurge in the mole fraction (α1) of NaB, indicating the non-ideality of the evaluated solution mixtures. The interaction parameter (β) was negative, revealing that the interaction between the constituents increased with the increasing α1 of NaB in aqueous solution. In the NaCl solution, the β value increased, whereas, in the U solution, the value decreased. The degree of dissociation (g) values decreased by increasing the α1 of NaB in the solution mixture. Various thermodynamic parameters were also evaluated in detail. The activity coefficient values in all cases were below unity, which further indicated the non-ideality of the system. The assessed excess free energy (∆GexRb) of the system was found to be negative in all cases, displaying the stability of the formed mixed micelles. Across the different solvents, their magnitudes were observed in the following order: ∆GexRb in NaCl > ∆GexRb in water >∆GexRb in U. An ultraviolet (UV)-visible study showed a clear interaction between NaB and PMT in the aqueous system. A Fourier-transform-infrared (FT-IR) spectroscopy investigation revealed a shift in the frequency bands of the components due to the interactions between them.

Conductivity method was carried out at various temperatures ranging from 293.15 K to 313.15 K to examine the monomeric as well as micellar phases of aqueous/brine/urea solutions of mixed systems composed of anionic surfactant sodium dodecyl sulfate (SDS) and cationic drug amitriptyline hydrochloride (AMT). AMT is used to treat mental/mood problems such as depression. NaCl decreases critical micelles concentration (cmc) of pure components as well as their mixed systems may be mainly ascribed to the salting-out effect of the hydrophobic moiety of components while urea increases the cmc value because of enhancement in the surface charge of the micelles/mixed micelles. The interaction among the monomers in the micelles/mixed micelles in the urea solution is slightly less than the NaCl and aqueous solutions. Synergism is modeled by employing the regular solution theory (RST) with a negative interaction parameter and nonideal behavior. Molecular thermodynamic models of Rubingh, Rodens and Motomura allow the calculation of the total excess free energy of micellization (ΔGex) with negative values in all the three situations. The aggregation number, micropolarity, and apparent dielectric constant of solution mixtures were evaluated and discussed in detail by fluorescence measurement in three different media.

Enormous phenotypic plasticity makes macrophages the target cells in obesity-associated inflammatory diseases. Thus, nutritional components that polarize macrophages toward antiinflammatory phenotype can partially reverse inflammatory diseases like insulin resistance. In the present study, macrophage-polarizing and insulin-sensitizing properties of fish oil (FO) were evaluated in obese insulin-resistant c57bl/6 mice fed high-fat diet (HFD-IR) after oral supplementation with FO (4, 8 or 16mg/kg body weight) and compared to lean and HFD-IR mice. FO-supplemented HFD-IR mice exhibited reduced adiposity index, serum cholesterol and triglycerides and increased insulin sensitization and showed improved adipose tissue physiology under light and transmission electron microscopy. NF-κB/P65 expression showed a downward shift on FO supplementation. The surface marker of M1 macrophages (CD-86) and the TLR-4 expression reduced with the increased supplementation of FO. Expression of arginase 1, an important marker of M2 macrophages, increased in a dose-dependent manner in response to FO dosage, which was observed at protein level by the western blotting and at mRNA level by real-time PCR. The cytokine profile of adipose tissue macrophages showed a steep shift toward antiinflammatory ones (IL-4 and IL-10) from the inflammatory TNF-α, IFN-γ, IL-2 and IL-1β. Thus, macrophage polarization seems to be the plausible mechanism via which FO alleviates obesity-induced inflammation and insulin resistance.

The desirable surface/bulk properties for specific applications of drug sodium salt of ibuprofen (IBF) and Triton X-100 (TX-100) can be achieved by adjusting mainly the composition of these systems. The interactions of anionic drug IBF with non-ionic surfactant TX-100 micelles have been investigated using tensiometry, fluorometry and 1H NMR in aqueous as well in 250 mmol⋅kg−1 urea solutions. Different theoretical models like Clint, Rubingh, and Rosen, etc. were utilized to get information about the nature of interaction between these two in bulk and at the interface. These models disclose that the non-ideal behavior with attractive interaction in bulk and at the interface exists. The steady-state fluorescence quenching study was employed to evaluate micelle aggregation numbers (Nagg), which signify the involvement of surfactant was forever higher compared to IBF. Stern–Volmer binding constants (Ksv), micropolarity (I1/I3) and dielectric constant (Dexp) of the mixtures are also obtained using fluorescence method. By the addition of urea raise in the surface charge of the micelles was observed followed by halt of the micellization of drug and surfactant as well as their mixture, therefore cmc values increases followed by decrease in aggregation number. The 1H NMR resonance intensity variations were paralleled by upfield shifts in the resonance frequencies, due to an increased shielding of IBF happening from closeness of the non-ionic TX-100 surfactant.

Herein, we have accounted the interaction of an antidepressant drug amitriptyline hydrochloride (AMT) with nonionic surfactant (TX-100) in aqueous solutions using different spectroscopic techniques. The difference in structure of the AMT and TX-100 surfactant also play a crucial role for the aggregational phenomena of the amphiphiles mixed systems. Critical micelle concentration (cmc) of different mixtures was evaluated from the I1/I3 versus total amphiphile concentration plots. cmc value of pure drug and TX-100 as well as their mixtures in different ratio were also computed by dye solubilization method using UV–visible spectrophotometer. The different physicochemical parameters, such as micellar mole fraction (X1Rub), activity coefficients (f1m, f2m), micropolarity, micelle aggregation number (Nagg), Stern–Volmer binding constants (Ksv) and dielectric constant (Dexp) have been evaluated for all solution mixture. Micelle aggregation numbers (Nagg) suggest that the involvement of TX-100 in the micelles was more than that of the AMT. Nuclear magnetic resonance (1H NMR) data of solution mixtures suggested that AMT and TX-100 interacts through hydrophobic interaction.

Protein tyrosine phosphorylation is a potent post-translational regulatory mechanism necessary for maintaining normal physiological functioning of immune cells and it is under the stringent control of antagonizing actions of Protein tyrosine phosphatases and kinases. Two such important Non-Receptor protein tyrosine phosphatases, SHP-1 and SHP-2, have been found to be expressed in immune cells and reported to be key regulators of immune cell development, functions, and differentiation by modulating the duration and amplitude of the downstream cascade transduced via receptors. They also have been conceded as the immune checkpoints & therapeutic targets and hence, it is important to understand their significance intricately. This review compares the roles of these two important cytoplasmic PTPs, SHP1 & SHP-2 in the regulation of peripheral as well as central immunity.

An evaluation of the interactions of cationic phenothiazine drug promazine hydrochloride (PMZ) with gelatin in aqueous solution as well as in the presence of 50 mM NaCl and 100 mM urea, investigated through different physicochemical measurements is presented in the present study using conductometric method. PMZ is used for the control of mania and schizophrenia. The drug interacts with gelatin similar to the interaction of surfactants and polymers. The plots of specific conductivity versus concentration of the drug were nonlinear with three different linear regions with two clear breaks. The first break point, i.e., critical aggregation concentration ( cac ), appeared well below the typical critical micelle concentration ( cmc ). The second break point is considered as polymer saturation point ( psp ) that is akin to cmc . The cac value decreases on increasing the gelatin concentration, whereas the psp value increases for all fixed concentrations (%w/v) of gelatin which is a clear signal of the interaction of the drug with gelatin. As inorganic salts increase the ionic strength, the solubility of amphiphile (drug) is lowered by ionic screening effects, ensuing in a greater tendency to aggregates at lower concentration. As a result, both the cac and psp / cmc values decrease. By the addition of urea an increase in the surface charge of the micelles was observed followed by halt of the aggregation of the drug hence both the cac and psp / cmc values increase. Free energies of aggregation (Δ G agg ), micellization (Δ G mic ), polymer saturation (∆ G psp ) and transfer (Δ G t ) were also evaluated.

Various additives viz. hydrotropes, bile salts, fatty acid and cyclodextrin effect on the cloud point (CP) behavior of amphiphilic drug promazine hydrochloride (PMZ) in 1 mmol dm−3 14-4-14 + 10 mmol dm−3 sodium phosphate (SP) buffer solutions have been investigated in the present study. These various additives are usually used as pharmaceutical excipients. The additives like anionic hydrotropes, bile salts and fatty acid salts increase the CP of PMZ, when added in low concentrations, whereas at high concentration, decrease it. Cationic and nonionic hydrotropes increase the CP of PMZ solutions at all concentration. Cyclodextrin behave like simple sugar is found to decrease the CP of the drug solutions at all concentrations. Gemini surfactant (14-4-14) has been found a better surfactant that can prevent clouding under physiological condition. It can thus be used as a drug-carrier system that increases the storage stability. The thermodynamic parameters are also evaluated: where Δ G c o is found to be negative and Δ H c o and T Δ S c o values are negative as well as positive depending upon type and nature of additive.

The effect of gelatin on the micellization behavior of amphiphilic drug nortriptyline hydrochloride (NOT) in aqueous as well as aqueous urea (250 mM) solutions has been studied using conductimetric technique. NOT is indicated for the relief of symptoms of depression. It is a tricyclic antidepressant drug. The drug interacts with gelatin similar to the interaction of surfactants and polymers. The plots of specific conductivity versus concentration of drug were nonlinear with three different linear regions with two clear breaks. The first break point, i.e., critical aggregation concentration (cac), appeared well below the typical critical micelle concentration (cmc). The second break point is considered as polymer saturation point (psp) that is similar to cmc. The cac value decreases on increasing the gelatin concentration, whereas psp value increases for all fixed concentrations (%, w/v) of gelatin which is a clear signal of the interaction of the drug with gelatin. Free energies of aggregation (ΔGagg) and micellization (ΔGmic) were also evaluated. In the presence of urea the increase in the surface charge of the micelles was observed followed by halt of the aggregation. Effect of NOT (drug) on the secondary structure of gelatin in aqueous solutions was also examined using CD measurements. The measurements verified that the random coil content of gelatin increases with increasing the NOT concentration.

The present study evaluated mineral compound, pearl in ashed form [PAF], for its potential as oral immunomodulator. ICP-MS, atomic absorption spectroscopy, CHNS analysis and XRD analysis were used for characterization of PAF. Surface antigen markers (TLR-2/4 and CD-80/86) were studied by flow cytometry. At dose concentration of 25, 50, 100 and 500 μg/kg body wt., administrated orally for 10 days, TLR-2 expression on murine peritoneal macrophage increased while TLR-4 expression was reduced as compared to control. There was an increase in OVA and mitogen (Con-A) specific lymphocyte proliferation in OVA immunized mice. Also, level of both Th1 (IL-2/IFN-γ) and Th2 (IL-4/IL-10) cytokines, and level and titer of total IgG, IgG1, IgG2a and IgG2b of OVA immunized mice significantly increased. The level of Inflammatory cytokines (IL-1β and TNF-α) did not increase significantly. Enhancement in T and B cell immune responses may be possibly due to significantly enhanced expression of CD-80 and CD-86 co-stimulatory signals as observed using flow cytometry. Also, enhanced phagocytic activity and DTH response exhibit stimulatory effect of PAF on innate and cell mediated immune response. Histopathological analysis of liver, kidney and spleen and analysis of other toxicity parameters, such as effect on body weight, lymphoid organ weight and cellularity, revealed PAF to exhibit no toxic effects. PAF seems to be a promising balanced Th1 and Th2 directing immunomodulator, possibly activating TLR2 through TIR domain-containing adaptor inducing interferon β (TRIF)-dependent pathway that leads to T-cell activation and promotes effective immune responses and may find useful application clinically.

The critical micelle concentration ( CMC ) of cationic gemini surfactant butanediyl-1, 4-bis(dimethyldodecylammonium bromide) with additives (primary linear alcohols (butanol, pentanol, hexanol) and primary linear amines (butylamine, pentylamine, hexylamine)) in presence of inorganic salt potassium nitrate is measured by surface tension measurements at 303 K in the present study. The CMC value of the gemini decreased with increasing concentration of additives and the extent of the effect observed was in the order: C 6 OH > C 5 OH > C 4 OH; C 6 NH 2 > C 5 NH 2 > C 4 NH 2 . The surfactant concentration required to reduce the surface tension of solvent by 20 mN m − 1 , C 20 , ratio of C 20 and CMC , maximum surface excess concentration at the air/solution interface, Γ max , and minimum area per surfactant molecule, A min , were evaluated. The interaction parameters β σ (for mixed monolayer formation at the solution/air interface), β m (for mixed micelle formation in aqueous medium) and f 1 m , f 2 m (activity coefficients) were also reported. As evident from interaction parameters, a synergistic interaction was observed both in the micelle as well as at the interface. Rubingh and Rosen models were used to evaluate the interaction parameters for the mixed micelles and at mixed monolayer, respectively. The ∆ G 0 m , standard free energy of micellization, and ∆ G 0 ads , free energy of adsorption, were also calculated.

AIMS: There is limited information characterizing young adults (18-35 years) (YA) with diabetes, especially those admitted for hyperglycemic emergencies. The study aims were to examine associations of patient-level characteristics with hyperglycemic emergency hospitalization and to identify variations based on diabetes type and glycemic control. METHODS: We conducted retrospective analysis of 273 YA admitted to an inner-city hospital with diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic nonketotic syndrome (HHS). T-tests, Chi-Square tests, and ANOVA identified differences in demographics, diabetes history, clinical indicators, complications/comorbidities, and hospital admission stratified separately by diabetes type (1 vs 2) and admission HbA1c

Interaction of amitriptyline hydrochloride (AMT), a tricyclic antidepressant amphiphilic drug, was seen with various polymers using conductometry, surface tensiometry and viscometry. Amphiphilic drug interacted with polymers in a surfactant like fashion. The plots of specific conductivity versus concentration of drug were nonlinear with three different linear regions and with two clear breaks. First break point, i.e., critical aggregation concentration (C 1 ), appeared well below the usual critical micelle concentration while polymer domain saturated at quite higher concentration (C 2 ). In case of surface tension measurements, the isotherms were composed of three identifiable points termed as T 1 , T 2 and T 3 . T 1 signaled the onset of the interaction, i.e., C 1 , while T 2 is regarded as the saturation of the polymer backbone. For weakly interacting polymers the surface tension isotherms were different from the strongly interacting polymers. Viscosity measurements suggest the relative size of the polymer-drug complex which changes differently for each polymer according to their nature of interactions. Free energies of aggregation (∆ G agg ) and micellization (∆ G mic ) were computed with the help of degrees of micelle ionization obtained from the specific conductivity — [AMT] plots.

Cisplatin (CP) is an effective chemotherapeutic agent widely used in the treatment of many malignant tumours. However, its therapeutic utility is limited by dose dependent nephrotoxicity. Several agents/strategies have attempted to prevent CP nephrotoxicity but were not found suitable for clinical practice. Dietary flaxseed oil (FXO), a rich source of omega-3 fatty acids has been shown to prevent/reduce the progression of certain types of cardiovascular and renal disorders. The protective effect of FXO on CP induced nephrotoxic and other deleterious effects was investigated. Rats were prefed experimental diets for 10 days and then received a single dose of CP (6 mg/kg body weight) intraperitoneally while still on diet. Serum/urine parameters, enzymes of brush border membrane (BBM), oxidative stress and carbohydrate metabolism in rat kidney were analyzed. CP nephrotoxicity was recorded by increased serum creatinine and blood urea nitrogen. CP decreased the activities of metabolic enzymes, antioxidant defense system and BBM enzymes. In contrast, FXO alone increased enzyme activities of carbohydrate metabolism and brush border membrane. FXO feeding to CP treated rats markedly enhanced resistance to CP-elicited deleterious effects. Dietary FXO supplementation ameliorated CP induced specific metabolic alterations and oxidative damage due to its intrinsic biochemical antioxidant properties.

Cyclodextrins are very well known to form the inclusion complexes with various drugs owing to their internal cavity. In this paper we have studied the interaction of β-cyclodextrin (β-CD) with amphiphilic drug amitriptyline hydrochloride (AMT) exploiting conductometry, surface tensiometry and viscometry. It was found that addition of β-CD to the drug solution causes the shifting of micellization of amphiphilic drug toward higher concentrations. This confirms the complex formation between the drug and the host molecule as a result of the interaction between them. Surface tension isotherms suggest that the addition of β-CD results in the surface tension of the solution to decrease as compared to the pure solution of drug due to the encapsulation of surface active drug inside the hydrophobic cavity of β-CD. Similarly, viscosity of the solution decreases drastically on the addition of β-CD which further increased on increasing the drug concentration. Free energy of micellization (∆Gmic) was computed with the help of degrees of micelle ionization obtained from the specific conductivity − [AMT] plots.

The effect of salts (inorganic and organic) on the characteristic solution properties of bis(quaternary ammonium) gemini surfactant butanediyl-1,4-bis(dimethyldodecylammonium bromide) (referred to as 12-4-12) was explored. The results showed that salt counterions induce synergistic effects and greatly enhance the efficiency of gemini in surface tension reduction as well as the ability of micellization. Furthermore, combinations of salt anions and gemini exhibited thickening of their aqueous solutions. The aggregate morphology is strongly dependent on the nature and size of the counterions. These were also attributed to the unique molecular structure of gemini surfactant, where the spacer (polymethylene chain) links the two quaternary ammonium head groups. The interaction and micellar growth of cationic gemini-salt systems with the inorganic salts have been found to obey Hofmeister series. Also, the anions of organic salts promote the hydrophobic interaction between the alkyl tails of gemini surfactant. In addition, the orientation of the substituents in the aromatic fragment is important too.

Background Studies assessing patch testing (PT) in allergy practices are limited. Objectives To determine whether PT results using a limited panel of allergens such as in the Thin-Layer Rapid-Use Epicutaneous Test (TT) as compared with an expanded panel, such as the addition of supplemental allergens (North American Contact Dermatitis [NACD] Panel, Dormer Cosmetics, hairdressing series, corticosteroid series, and personal products) will miss a significant number of positive PTs. To compare our PT results with published data from dermatology practices. Methods This is a 5-year multicenter retrospective chart review of PT at 3 separate allergy practices. Results Four hundred twenty-seven patients (mean age, 49.8 years) were patch tested. Eighty-two percent were female; 54% reported an atopic history. Of the standardized allergens, the 5 most common positives were nickel sulfate, fragrance mix I, p-phenylenediamine (PPD), thimerosal, and cobalt chloride. Two hundred eighteen (56.9%; 95% CI=51.9–61.8%) patients were positive to at least 1 TT allergen. Ninety-eight (25.6%; 95% CI=21.5–30.2%) patients were positive to both a TT and a supplemental allergen. Forty-eight (12.5%; 95% CI=9.6–16.2%) patients were negative to a TT allergen but positive to a supplemental allergen. Conclusion Positive allergens would have been missed in 12.5% of patients when evaluating with TT allergens alone, whereas 25.6% would be partially evaluated. Patch test performance characteristics for these allergy practices appear to parallel that seen for dermatology. The TT remains an adequate screening tool in an allergy practice, but a more comprehensive panel may be needed to fully evaluate contact dermatitis.

Human and animal exposure demonstrates that uranium is nephrotoxic. However, attempts to reduce it were not found suitable for clinical use. Dietary fish oil (FO) enriched in omega-3 fatty acids reduces the severity of cardiovascular and renal diseases. Present study investigates the protective effect of FO on uranyl nitrate (UN)-induced renal damage. Rats prefed with experimental diets for 15 days, given single nephrotoxic dose of UN (0.5mg/kg body weight) intraperitoneally. After 5d of UN treatment, serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM), oxidative stress and phosphate transport were analyzed in rat kidney. UN nephrotoxicity was characterized by increased serum creatinine and blood urea nitrogen. UN increased the activity of lactate dehydrogenase and NADP-malic enzyme whereas decreased malate, isocitrate and glucose-6-phophate dehydrogenases; glucose-6-phophatase, fructose-1, 6-bisphosphatase and BBM enzyme activities. UN caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation, activities of superoxide dismutase, glutathione peroxidase and decreased catalase activity. Feeding FO alone increased activities of enzymes of glucose metabolism, BBM, oxidative stress and Pi transport. UN-elicited alterations were prevented by FO feeding. However, corn oil had no such effects and was not similarly effective. In conclusion, FO appears to protect against UN-induced nephrotoxicity by improving energy metabolism and antioxidant defense mechanism.

Uranium, the heaviest of the naturally occurring elements is widely present as environmental contaminant from natural deposits, industrial emissions and most importantly from modern weapons. Histopathological examinations revealed that uranyl nitrate (UN) exposure caused severe damage to pars recta of renal proximal tubule. However, biochemical events involved in cellular response to renal injury are not completely elucidated. We hypothesized that UN exposure would severely damage kidney tissues and alter their metabolic functions. Rats were treated with a single nephrotoxic dose of UN (0.5 mg/kg body weight) i.p. After 5 d, effect of UN was studied on the activities of various enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in different kidney tissues. Activity of lactate dehydrogenase increased whereas activities of isocitrate, succinate and malate dehydrogenases, glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly decreased by UN exposure. Activity of glucose-6-phosphate dehydrogenase decreased whereas that of NADP-malic enzyme increased. The activities of BBM enzymes were significantly lowered and after dissociation from BBM excreted in urine. Lipid peroxidation and the activities of superoxide dismutase and glutathione peroxidase increased whereas catalase activity decreased by UN. UN treatment caused specific alterations in the activities of metabolic and membrane enzymes and perturbed antioxidant defenses.

The use of free tissue transfers has dramatically improved the outcomes of soft tissue reconstructions of the face. This is particularly true when large volumes of soft tissue are needed or when the recipient bed has a compromised local blood supply. Although traditional fat grafting procedures often allow for satisfactory results in some patients, the use of scapular and parascapular free tissue transfers has markedly improved the predictability of these reconstructions, often in a single stage. As perforator flap reconstructions evolve over time, these types of flaps may eventually supplant the available fasciocutaneous free flaps as the flap of choice in these reconstructions primarily because of improved donor site scarring and morbidity.