ANTICANCER MEDICINES (DOXORUBICIN AND METHOTREXATE) CONJUGATED WITH MAGNETIC NANOPARTICLES FOR TARGETING DRUG DELIVERY THROUGH IRON

The uptake of iron is increased by cancer cells. Iron magnetic nanoparticles (MNP) can be used as a nanovehicle for immobilization of anticancer medicines and to integrate them at a target site. The anticancer medicines doxorubicin (DOX) and methotrexate (MTX) were immobilized separately and in combination onto MNP by a glutaraldehyde activation method and confirmed by magnetic nanoparticles linked immunosorbent assay (MagLISA) and Fourier-transform infrared (FTIR) spectroscopy. The phenol peaks of DOX and MTX at 2896.6 cm^?1 to 2912.5 cm^?1 in FTIR spectra of immobilized medicines indicated the conjugation. Affinity-purified anti-DOX and anti-MTX antibodies were used to evaluate the coupling of DOX and MTX onto MNP, and the binding was found 34.6% to 37.2% and 51.8% to 54.3% separately, respectively. The immobilization of DOX and MTX in combination onto MNP was 18% and 27%, respectively. HeLa and B cells were cultured with DOX-MNP, MTX-MNP, and DOX-MNP-MTX separately, and MagLISA indicated that the binding of DOX-MNP/MTX-MNP was 41.5% to 45% with HeLa cells and 20% to 26% with B cells. No significant difference was observed in binding of DOX-MNP-MTX with HeLa and B cells. Results also indicated that the release of medicines at pH 5.0 is more (39% to 44%) than at pH 7.4 (3.7% to 10.2%). Sixteen to 22% more killing effect was observed on HeLa cells than on B cells. In immunohistochemical staining, more deposition of brown color on HeLa cells than on B cells may be due to more expression of iron-binding sites on cancer cells. The dual property of MNP can be used for binding of medicines and for targeting drug delivery.     

Evaluation of Toxic Risk Assessment of Arsenic in Male Subjects Through Drinking Water in Southern Sindh Pakistan

The arsenic (As) hazardous quotient was estimated based on concentration of As in drinking water and scalp hair of male subjects of two age groups (n = 360) consuming As contaminated water at different levels and non-contaminated drinking water. The total As concentrations in drinking water of less-exposed (LE) and high-exposed (HE) areas was found to be 3- to 30-fold higher than the permissible limit of the World Health Organization (2004) for drinking water, while the levels of As in drinking water of non-exposed (NE) areas was within the permissible limit. The levels of As in scalp hair samples of male subjects of two age groups belonging to NE, LE, and HE areas ranged from 0.01 to 0.27, 0.11–1.31, and 0.36–6.80 μg/g, respectively. A significant correlation between As contents of drinking water and As concentration in scalp hair was observed in sub-district Gambit (r = 0.825–0.852, p < 0.001) as compared to those subjects belonging to LE sub-district Thari Mirwah. A toxicity risk assessment provides a hazard quotient corresponding to <10 that indicates non-carcinogenic exposure risk of understudy areas.     

Evaluation of Cadmium, Chromium, Nickel, and Zinc in Biological Samples of Psoriasis Patients Living in Pakistani Cement Factory Area

Psoriasis is a noncontiguous common and chronic skin disorder. The aim of the present study was to compare the level of trace elements cadmium (Cd), chromium (Cr), Nickel (Ni), and zinc (Zn) in biological samples (whole blood, urine, and scalp hair) of psoriasis patients of both gender age ranged (25–55 years) at mild, moderate severe, and more severe stage (n?=?418) living in the vicinity of cement factory. For comparison purposes, healthy age-matched referent subjects, residents of industrial and non-industrial area, of both gender were also selected (n?=?241). The concentrations of trace and toxic elements were measured by atomic absorption spectrophotometer prior to microwave-assisted acid digestion. The validity and accuracy of methodology was checked by using certified reference materials (CRMs) and conventional wet acid digestion method on same CRMs and real samples. The results of this study showed that the mean values of Cd, Cr, Ni, and Pb were significantly higher in scalp hair, blood, and urine samples of mild and severe psoriasis patients as compared to referents (p?<?0.001), while the concentration of Zn was lower in the scalp hair and blood, but higher in the urine samples of psoriasis patients. The deficiency of Zn in psoriasis patients may be undoubtedly caused by the toxic element exposures via cement factory.     

Evaluation of Status of Cadmium, Lead, and Nickel Levels in Biological Samples of Normal and Night Blindness Children of Age Groups 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood trace metals toxicity, which is the most common problem found in underdeveloped countries. This study was designed to compare the levels of cadmium (Cd), lead (Pb), and nickel (Ni) in scalp hair, blood, and urine of night blindness children age ranged 3–7 and 8–12 years of both genders, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of Cd, Pb, and Ni in biological samples of night blindness children. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cd, Pb, and Ni by electrothermal atomic absorption spectrometry. The results indicated significantly higher levels of Cd, Pb, and Ni in the biological samples (blood, scalp hair, and urine) of male and female night blindness children, compared with control subjects of both genders. These data present guidance to clinicians and other professional investigating toxicity of trace metals in biological samples of night blindness children.     

Evaluation of Status of Zinc, Copper, and Iron Levels in Biological Samples of Normal Children and Children with Night Blindness with Age Groups of 3–7 and 8–12 Years

The causes of night blindness in children are multifactorial, and particular consideration has been given to childhood nutritional deficiency, which is the most common problem found in underdeveloped countries. Such deficiency can result in physiological and pathological processes that in turn influence hair composition. This study was designed to compare the levels of zinc (Zn), copper (Cu), and iron (Fe) in scalp hair, blood, and urine of both genders of children with night blindness with age range of 3–7 and 8–12 years, comparing them to sex- and age-matched controls. A microwave-assisted wet acid digestion procedure was developed as a sample pretreatment, for the determination of zinc, copper, and iron in biological samples of children with night blindness. The proposed method was validated by using conventional wet digestion and certified reference samples of hair, blood, and urine. The digests of all biological samples were analyzed for Cu, Fe, and Zn by flame atomic absorption spectrometry using an air/acetylene flame. The results indicated significantly lower levels of Fe, Cu, and Zn in the biological samples (blood and scalp hair) of male and female children with night blindness, compared with control subjects of both genders. These data present guidance to clinicians and other professionals investigating the deficiency of essential trace metals in biological samples (scalp hair and blood) of children with night blindness.     

Correlation Between Arsenic Concentration in Fish and Human Scalp Hair of People Living in Arsenic-Contaminated and Noncontaminated Areas of Pakistan

The effects of arsenic (As) toxicity due to frequent consumption of arsenic-contaminated fish was estimated by the analysis of scalp hair of adult males, living near arsenic-contaminated area of Pakistan. For comparison purposes, scalp hair samples were also collected from the inhabitants of Hyderabad city consuming fish species with low levels of As, collected from Indus River. Concentration of As in scalp hair samples was analyzed by using hydride generation atomic absorption spectrometry (HG AAS), after microwave-assisted acid digestion. The accuracy of the As measurement was tested simultaneously analyzing certified reference material. The concentration of As in muscle tissues of fish species were found in the range of 2.11 to 14.1?μg/g and 1.92 to 12.2?μg/g, collected from arsenic-contaminated and noncontaminated areas, respectively. Exposed subjects had significantly elevated levels of As in scalp hair samples (0.72-4.94?μg/g) as compared with referent subjects (0.21-1.484?μg/g; p?相似文献   

Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α

Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst assay. Bergenin was isolated from the crude extract of Mallotus philippenensis after repeated column chromatography and was then subjected to chemical derivatization. The structures of all compounds were elucidated by NMR and mass spectroscopic techniques. Compound 2 was also studied using single crystal X-ray diffraction. Compounds 4, (54.5±2.2%) 5 (47.5±0.5%) 5, and 15 (86.8±1.9%) showed significant (P≤0.005) NO inhibitory activities whereas 6, 7, 11, 12 and 13 displayed moderate inhibitory activities that ranges between 16% and 31%. Furthermore compounds 4 and 15, were discovered as significant (P≤0.005) TNF-α inhibitors with 98% and 96% inhibition, respectively, while compounds 3, 5, 7, 8, 11, and 12 showed low level of TNF-α inhibition (0.4-28%). Compounds 8, 13 and 15 exhibited moderate anti-inflammatory IC(50) activities with 212, 222, and 253 μM, respectively, compared to the standard anti-inflammatory drug indomethacin as well as the parent bergenin compound. No cytotoxic effects could be detected when the compounds were tested on 3T3 cells up to concentrations of 100 μM.     

Determination of Copper and Iron in Biological Samples of Viral Hepatitis (A–E) Female Patients

There is accumulative evidence that the metabolism of iron and copper is altered in viral hepatic diseases, and these nutrients might have specific roles in their pathogenesis and progress. The aim of present study was to compare the level of copper (Cu) and iron (Fe) in biological samples (serum, urine, and scalp hair) of female patients suffering from different viral hepatitis (A, B, C, D, and E; n?=?253) of age range 31–45 years. For comparative study, 95 healthy females of the same age group residing in the same city were selected. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in sera and scalp hair samples of hepatitis patients than age-matched control subjects, while the difference was significant (p?<?0.001), in the cases of viral hepatitis B and viral hepatitis C as compared to viral hepatitis A, D, and E. The urinary levels of these elements were found higher in the hepatitis patients than in the age-matched healthy controls (p?<?0.05). These results are consistent with literature-reported data, confirming that hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.     

Animal cloning applications and issues

Significant progress in the field of biotechnology has allowed for the use of cloning in animals which is being used: to improve genetic makeup, to rescue endangered species, in tissue engineering and to increase farm animal population. Unfortunately, cloning has been met with failure due to a variety of reasons namely early and late abortions, compromised immune systems, circulatory and respiratory problems and a high rate of fetal death. The reasons of these problems are unknown, but may research groups are attempting to understand the underlying molecular and cellular mechanisms involved in cloning efficiency. Atypical epigenetic re-programming appears to be the primary cause of ineffective cloning. Understanding molecular mechanisms involving key regulatory proteins is pivotal in the success of animal cloning. This review shows the current paradigm involving animal cloning efficiency, and also further elucidates applications to improve animal cloning efficiency.     

Potassium, Calcium, Magnesium, and Sodium Levels in Biological Samples of Hypertensive and Nonhypertensive Diabetes Mellitus Patients

There is accumulating evidence that the metabolism of several essential elements is altered in diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progress of this disease. The aim of the present study was to compare the level of essential elements, potassium (K), calcium (Ca), magnesium (Mg), and sodium (Na), in biological samples (whole blood, urine, and scalp hair) of patients who have hypertensive diabetes mellitus type 2 (n = 254) and nonhypertensive diabetes mellitus type 2 (n = 228) with those of nondiabetic as control subjects (n = 182; age range of both genders 45-75). The element concentrations were measured by means of an atomic absorption spectrophotometer after microwave-induced acid digestion. The validity and accuracy was checked by conventional wet acid digestion method and using certified reference materials. The overall recoveries of all elements were found in the range of 99.1-99.9% of certified values. The results of this study showed that the mean values of K, Mg, and Ca were significantly reduced, while Na level were higher in blood and scalp hair samples of hypertensive diabetic (HD) patients and nonhypertensive diabetic (NHD) patients as compared to control subjects of both genders (p < 0.05), but level of K in the biological samples of nonhypertensive diabetic patient was found to be higher, but it was not significant (p = 0.05).The urinary levels of these elements were found to be higher in both HD and NHD patients than in the age-matched healthy controls. These results are consistent with those obtained in other studies, confirming that deficiency and efficiency of some essential trace metals may play a role in the development of diabetes mellitus.