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1.
Plants (Basel) ; 13(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38999685

ABSTRACT

Gray mold, caused by Botrytis cinerea Pers. Fr., is one of the most vital plant diseases, causing extensive pre- and post-harvest losses in apple fruits. In the current study, we isolated and identified two potential endophytic bioagents, Bacillus subtilis and Streptomyces endus. Both bioagents exhibited a potent fungistatic effect against B. cinerea under both in vitro and in planta conditions. Moreover, two experiments were carried out; (i) the first experiment was conducted at room temperature after artificial inoculation with B. cinerea to monitor the progression of the infection and the corresponding biochemical responses of the apples. Our in vivo findings showed that the treated B. cinerea-infected apple fruits with the cell-free bacterial filtrate of B. subtilis and S. endus (dipping or wrapping) significantly reduced the rotten area of the treated apple at room temperature. Additionally, B. subtilis and S. endus enhanced the enzymatic (POX and PPO) and non-enzymatic (phenolics and flavonoids) antioxidant defense machinery in treated apples. (ii) The second experiment focused on the preventive effects of both bioagents over a 90-day storage period at 1 °C of healthy apples (no artificial inoculation). The application of both bacterial filtrates prolonged the storage period, reduced the relative weight loss, and maintained high-quality parameters including titratable acidity, firmness, and total soluble solids of apple fruits under cold storage at 1 °C. The Kaplan-Meier analysis of rotten apples over 90 days during cold storage showed that the treated apples lasted longer than the non-treated apples. Moreover, the lifespan of apple fruits dipped in the culture filtrate of B. subtilis, or a fungicide, was increased, with no significant differences, compared with the non-treated apples. The current results showed the possibility of using both bioagents as a safe and eco-friendly alternative to chemical fungicides to control gray mold disease in apples.

2.
Cells ; 12(22)2023 11 17.
Article in English | MEDLINE | ID: mdl-37998379

ABSTRACT

Eight wheat cultivars, Sakha-94, Giza-171, Sids-1, Sids-12, Sids-13, Shandweel-1, Misr-1, and Misr-2, were evaluated for leaf rust at the seedling and adult stages in the 2021 and 2022 seasons. Biochemical, histological, and genetic analyses were performed to determine the link between cultivars that were either sensitive or resistant to the disease. Misr-2 and Giza-171 cultivars had the highest levels of resistance to leaf rust races in 2021 (LTCGT, STSJT, and TTTST) and 2022 (MBGJT, TTTKS, and TTTTT) at the seedling stage. However, at the adult stage, Sakha-94, Giza-171, Misr-1, and Misr-2 cultivars had the highest levels of resistance; consequently, they had the lowest final disease severity and the lowest values of AUDPC. The correlation between the seedling reaction and adult reaction was non-significant, with values of 0.4401 and 0.4793 in the 2021 and 2022 seasons, respectively. Throughout the biochemical, histological, and genetic analyses, it was observed that catalase, peroxidase, and polyphenol oxidase activities significantly increased in the resistant cultivars. The discoloration of superoxide (O2-) and hydrogen peroxide (H2O2) significantly decreased in resistant and moderately resistant wheat cultivars (Sakha-94, Giza-171, Misr-1, and Misr-2); higher hydrogen peroxide (H2O2) and superoxide (O2-) levels were recorded for the susceptible cultivars compared to the resistant cultivars. Molecular markers proved that the Lr50 gene was detected in the resistant cultivars. Puccinia triticina infections negatively affected most histological characteristics of flag leaves, especially in susceptible cultivars. The thickness of the blade (µ), the thickness of the upper and lower epidermis (UE and LE), the thickness of mesophyll tissue (MT), and bundle length and width in the midrib were decreased in susceptible cultivars such as Sids-1, Sids-13, and Shandwel-1 compared with resistant cultivars.


Subject(s)
Basidiomycota , Triticum , Triticum/genetics , Triticum/microbiology , Antioxidants , Hydrogen Peroxide , Superoxides , Plant Diseases/genetics , Plant Diseases/microbiology
3.
Eur Rev Med Pharmacol Sci ; 27(11): 5200-5210, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37318494

ABSTRACT

OBJECTIVE: Some studies have shown that metformin inhibits the proliferation of breast cancer (BC) cells via multiple ways. One of these mechanisms is through the indirect control of the IGF-route mediated via the activation of the AMPK-LKB1 pathway in the liver, which leads to a decrease in blood glucose and insulin levels. The objective of this study was to investigate the effects of metformin as adjuvant to chemotherapy on IGF levels in female patients with progressive and non-progressive metastatic BC. PATIENTS AND METHODS: In this trial, 107 women receiving chemotherapy for metastatic breast cancer (MBC) were divided into two groups: the metformin group received 500 mg of metformin twice daily, whereas the control group did not receive any metformin. All patients received chemotherapy according to the South Egypt Cancer Institute's (SECI) established regimen. The level of IGF-1 was determined in the blood at the initiation of therapy (baseline) and at six months post treatment. RESULTS: No substantial differences were noted regarding IGF-1 levels in both groups at baseline (IGF-1 average level was 40.74 ± 36.16 vs. 32.06 ± 20.00 in the metformin and the placebo group, respectively, p = 0.462). While after six months, the mean IGF-1 level was 37.62 ± 31.35 vs. 39.12 ± 2 5.93 in the metformin and placebo groups, respectively, (p = 0.170). CONCLUSIONS: Metformin as an adjuvant to chemotherapy in MBC patients had no significant effect on reducing IGF-l levels which promotes the inhibition of the proliferation of BC cells in MBC patients.


Subject(s)
Breast Neoplasms , Metformin , Humans , Female , Metformin/pharmacology , Breast Neoplasms/pathology , Insulin-Like Growth Factor I/therapeutic use , Blood Glucose/metabolism , Adjuvants, Immunologic/therapeutic use , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use
4.
Plants (Basel) ; 11(23)2022 Nov 27.
Article in English | MEDLINE | ID: mdl-36501297

ABSTRACT

Powdery mildew disease, caused by Erysiphe betae, is one of the most threatening diseases on sugar beet plants worldwide. It causes a great loss in the root yield, sugar percentage, and quality of produced sugar. In the current study, we aimed to evaluate the susceptibility of 25 sugar beet cultivars to infection with powdery mildew disease under Egyptian conditions. Moreover, we evaluated the impacts of three eco-friendly materials, including potassium bicarbonate (KHCO3; at 5 and 10 g L-1), Moringa oleifera seed extract (25 and 50 g L-1), and the biocontrol agent, Bacillus subtilis (108 cell suspension) against E. betae in two successive seasons 2020 and 2021. Our findings showed that there were significant differences between these 25 cultivars in their susceptibility to the disease under study. Using the detached leaves technique in vitro, B. subtilis showed strong antifungal activity against E. betae. Moreover, both concentrations of KHCO3 and moringa seed extract significantly reduced the disease severity. Under field conditions, tested treatments significantly reduced the severity of powdery mildew disease and prevented E. betae from producing its conidiophores and conidia. Scanning electron microscope examination of treated leaves demonstrated the presence of the decomposition of fungal hyphae, conidiophores, conidia, and the occurrence of plasmolysis to fungal cells and spores on the surface of the leaves. Furthermore, these treatments greatly improved the percent of sucrose and soluble solids content, as well as the enzymatic activity of peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase. It is noteworthy that treatment with moringa seed extract gave the best results, followed by potassium bicarbonate, then B. subtilis cell suspension. Generally, it is recommended to use the substances used in this research to combat powdery mildew to minimize or prevent the use of chemical fungicides harmful to public health and the environment.

5.
J Clin Med ; 11(19)2022 Sep 20.
Article in English | MEDLINE | ID: mdl-36233373

ABSTRACT

BACKGROUND: Metformin has been reported to have an anti-tumorigenic impact against metastatic breast cancer (MBC) cells through several mechanisms. Its effect can be evaluated by using many variables such as the response rate (RR) as well as the progression-free survival (PFS). MATERIALS AND METHODS: A prospective study was conducted to investigate and estimate the metformin effect on MBC. About 107 subjects were included in the study and were divided into two groups: Group A included non-diabetic MBC patients treated with metformin in conjunction with chemotherapy and group B included those treated with chemotherapy alone. Both PFS and RR were used as a criteria to evaluate the treatment outcome. Associated adverse effects of metformin were also assessed. RESULTS: The average age of the participants in group A and group B was 50 vs. 47.5, respectively. No significant differences were detected between both cohorts concerning RR levels (regression disease (RD) 27.8% vs. 12.5%, stationary disease (SD) 44.4% vs. 41.7%, progression disease (PD) 27.8% vs. 45.8%, respectively, p = 0.074). Moreover, PFS showed no significant difference between both groups (p = 0.753). There was no significant correlation between metformin concentration and their adverse effects on the study participants. CONCLUSION: Metformin as an adjuvant therapy to MBC undergoing chemotherapy showed no significant survival benefit as determined by RR and PFS.

6.
Saudi J Biol Sci ; 29(4): 2219-2229, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35531157

ABSTRACT

Cercospora leaf spot caused by Cercospora beticola are among the most dangerous plant diseases on sugar beet plants. It causes heavy economic losses, whether on the yield of roots, the percentage of sugar in them, or the quality of sugar produced. In addition to the economic cost caused by chemical control, these chemical pesticides cause an imbalance in the ecosystem and harm the health of humans and animals. In an attempt to search for a safer method than pesticides and environmentally friendly, an evaluation of using biocontrol agents, Bacillus subtilis as cell suspension (108 cell/ml), was conducted in this study. Seeds extract of Moringa oleifera with two concentrations (25 and 50 g/L) and potassium bicarbonate at (5 and10 g/L (compared to fungicide Montoro 30% EC (Propiconazole 15% + Difenoconazole 15%). The evaluation results for twenty-five sugar beet varieties showed a significant discrepancy between these varieties in the extent of their susceptibility to infection with the disease under investigation. In-Vitro, B. subtilis induced an antagonist to C. beticola, and both M. oleifera seeds extract and potassium bicarbonate significantly reduced the linear growth of this pathogen. Under field conditions, the treatments used have given positive results in controlling Cercospora leaf spots. They significantly decreased the severity of disease and prevented C. beticola from creating conidiophores and conidiospores, along with examining their cell walls with the formation of plasmolysis of the fungus cells and reducing both the number and diameter of the spots on the surface leaves; this was demonstrated using a scanning electron microscope (SEM). It is worth noting that the best results obtained were most often when treated with M. oleifera seeds extract, followed by potassium bicarbonate, then cell suspension of B. subtilis. In addition, the percentage of the content of beet roots from total soluble solids and sucrose has improved significantly due to spraying sugar beet plants with the substances mentioned earlier. These treatments also contributed to a significant improvement in the enzymes polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase.

7.
Rev. esp. investig. quir ; 22(1): 11-14, 2019. tab
Article in English | IBECS | ID: ibc-184271

ABSTRACT

Background: Laparoscopic sleeve gastrectomy (LSG) is essentially a restrictive bariatric operation. Weight loss is achieved by drastically reducing the gastric volume, which in turn leads to reduced food intake. In addition, a series of hormonal changes occurring postoperatively in bariatric patients, contribute to decreased appetite, reduced food intake and long-term weight loss. To date there is a lack of standardization regarding the surgical technique of LSG, which may affect the long-term outcome of the patients. Our study aimed to assess the difference in short and long- term weight loss and complications between antral resection in laparoscopic sleeve gastrectomy and classical laparoscopic sleeve gastrectomy with antral preservation. Patients and Methods: This is a controlled clinical trial held in Ain Shams University Hospital including 40 patients with BMI >30, of them 20 underwent antral resection in laparoscopic sleeve gastrectomy, and the other 20 patients underwent classical laparoscopic sleeve gastrectomy, with antral preservation. Results: Our study showed mild increase in weight loss and BMI reduction after 12 months in the antral resection group compared with the antral preservation group with mean weight loss 70.5kg in antral resection group versus 75.05kg in antral preservation group and mean BMI 27.7% in antral resection group versus 27.9% in antral preservation group, but did not reach statistical significant values. Conclusion: Our study showed that antral resection in laparoscopic sleeve gastrectomy resulted in non-significant better weight loss in the first postoperative year than classical laparoscopic sleeve gastrectomy


No disponibe


Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Laparoscopy/methods , Gastrectomy/methods , Obesity/surgery , Bariatric Surgery/methods , Weight Loss , Treatment Outcome
8.
Cancer Radiother ; 22(3): 236-240, 2018 May.
Article in English | MEDLINE | ID: mdl-29678595

ABSTRACT

PURPOSE: A prospective phase II study carried out to evaluate hypofractionated radiotherapy with concurrent gemcitabine for bladder preservation in the elderly patient with bladder cancer. PATIENTS AND METHODS: Thirty-one patients were enrolled, age ≥65years, diagnosed with transitional cell carcinoma of the urinary bladder, after a maximum safe transurethral resection of a bladder tumour. They received 52.5Gy in 20 fractions using 3D conformal radiotherapy with concurrent 100mg/m2 gemcitabine weekly as a radiosensitizer. RESULTS: All patients completed their radiation therapy course, while seven patients received their chemotherapy irregularly due to grade 3 toxicities. Twenty-five patients (80.6%) achieved a complete response. At 2-years, overall survival was 94.4% and disease-free survival was 72.6%. T3 and residual after transurethral resection are factors that adversely affect disease-free survival. CONCLUSION: Hypofractionated radiotherapy and gemcitabine as a radiosensitizer in elderly as organ preservation for transitional cell carcinoma bladder cancer have acceptable toxicity profile with good response rate and disease-free survival, keeping salvage cystectomy for persistence or recurrence of invasive cancer.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Cystectomy , Deoxycytidine/analogs & derivatives , Radiation Dose Hypofractionation , Urinary Bladder Neoplasms/therapy , Aged , Aged, 80 and over , Combined Modality Therapy , Cystectomy/methods , Deoxycytidine/therapeutic use , Female , Humans , Male , Prospective Studies , Urethra , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/surgery , Gemcitabine
9.
Andrologia ; 50(2)2018 Mar.
Article in English | MEDLINE | ID: mdl-28771785

ABSTRACT

Reference values of WHO 1999 manual were used for the interpretation of semen analysis until 2010 when new reference values were introduced which have lower cut-off compared to WHO 1999. Therefore, several men who previously were diagnosed abnormal based on their semen analysis have now become normal using new reference values. This study was conducted on semen analyses of 661 men from Middle East region and Pakistan. All semen analyses were reviewed using WHO 1999 and WHO 2010 criteria. Results showed that based on new criteria, 19% of the population changed classification from abnormal to normal when all normal semen parameters were considered. When at least one or more abnormal semen parameters were considered, of the total 661, 44% (288) of the population changed its classification from abnormal to normal with shift from WHO 1999 to 2010 criteria. These findings show that using new cut-off values, many more men are considered normal, but using old criteria (WHO 1999), the same men would be classified as abnormal. This warrants further discussion over the investigations and management plans for patients whose semen analyses fall below WHO 1999 but above WHO 2010 cut-offs.


Subject(s)
Infertility, Male/diagnosis , Semen Analysis/trends , World Health Organization , Age Factors , Humans , Infertility, Male/physiopathology , Male , Middle East , Pakistan , Reference Values , Retrospective Studies , Semen/physiology , Semen Analysis/methods , Spermatozoa/physiology
10.
Bone Joint J ; 99-B(6): 774-778, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28566396

ABSTRACT

AIMS: The aim of this study was to report the outcome of the non-operative treatment of high-grade posterior cruciate ligament (PCL) injuries, particularly Hughston grade III injuries, which have not previously been described. PATIENTS AND METHODS: This was a prospective study involving 46 consecutive patients who were athletes with MRI-confirmed isolated PCL injuries presenting within four weeks of injury. All had Hughston grade II (25 athletes) or III (21 athletes) injuries. Our non-operative treatment regimen involved initial bracing, followed by an individualised rehabilitation programme determined by the symptoms and physical signs. The patients were reviewed until they had returned to sports-specific training, and were reviewed again at a mean of 5.2 years (3 to 9). RESULTS: The mean time to return to sports-specific training was 10.6 weeks and the mean time to return to full competitive sport was 16.4 weeks (10 to 40). A total of 42 patients (91.3%) were playing at the same or higher level of sport two years after the injury, with a mean Tegner activity score of 9 (5 to 10). At five years, 32 patients (69.5%) were playing at the same or higher level of sport, and 38 patients (82.6%) were playing at a competitive level, with a mean Tegner activity score of 9 (5 to 10). CONCLUSIONS: Medium-term review of a series of athletes suggests that commencing the non-operative management of isolated, Hughston grade II and III PCL injuries within four weeks of injury gives excellent functional outcomes with a high proportion returning to the same or higher level of sport. Cite this article: Bone Joint J 2017;99-B:774-8.


Subject(s)
Athletic Injuries/rehabilitation , Knee Injuries/rehabilitation , Posterior Cruciate Ligament/injuries , Return to Sport , Acute Disease , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Recovery of Function , Time Factors , Trauma Severity Indices , Treatment Outcome , Young Adult
11.
Andrologia ; 48(10): 1125-1129, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26847036

ABSTRACT

This hospital-based, prospective study was conducted to evaluate the relationship between body mass index (BMI) and various semen parameters in infertile men. A total of 439 men presented for infertility evaluation were assessed by basic infertility evaluation measures including semen analysis and BMI calculation. The main outcome measure was the relationship between BMI groups [BMI: 18.5-24.9 kg/m2 (normal weight), 25-29.9 kg/m2 (overweight) and ≥30 kg/m2 (obese)] and different semen parameters [volume, concentration, motility and morphology]. The mean BMI was 29.67 ± 5.89. Most of patients (82.91%) were overweight or obese. The 3 BMI groups were comparable in semen parameters (P > 0.05). BMI had a negative correlation with various semen parameters. However, this correlation was significant only with sperm concentration (P = 0.035). We concluded that sperm concentration was the only semen parameter which showed significant reduction with higher BMI in infertile men.


Subject(s)
Body Mass Index , Infertility, Male/physiopathology , Sperm Motility/physiology , Spermatozoa/cytology , Adult , Cell Shape/physiology , Humans , Male , Obesity/physiopathology , Overweight/physiopathology , Prospective Studies , Semen Analysis , Sperm Count
12.
Ann R Coll Surg Engl ; 93(7): 537-41, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22004637

ABSTRACT

INTRODUCTION: The aim of this study was to compare the functional outcome between the first and second knee replacement in patients undergoing staged bilateral total knee arthroplasty. METHODS: We identified 64 patients who had bilateral knee replacements and had at least one year of postoperative outcome studies. Data on pain scores, walking ability, use of walking aids, range of movement, instability, muscle strength, WOMAC® (Western Ontario and McMaster Universities) scores, SF-12 (Short Form 12) scores, American Knee Society radiological scores and length of hospital stay (LOS) were recorded. The difference in data between the first and second knee was assessed. RESULTS: Groups remained statistically comparable between the first and second operation. Four outcomes showed a significant difference between the second and first knee. The mean score for postoperative walking ability was 4.83 (second knee) vs 4.51 (first knee) (p =0.03). The mean score for postoperative walking aid requirement was 5.73 (second knee) vs 5.46 (first knee) (p=0.01). The mean postoperative SF-12 score was 54.26 (second knee) vs 52.45 (first knee) (p=0.04). The mean LOS was 4.73 days (second knee) vs 6.16 days (first knee) (p =0.05). All other data comparisons were statistically insignificant. CONCLUSIONS: Patients have a reduced LOS and continue to improve after the second procedure with regards to walking ability, use of walking aids and psychological wellbeing.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Osteoarthritis, Knee/surgery , Aged , Female , Humans , Length of Stay , Male , Middle Aged , Muscle Strength/physiology , Osteoarthritis, Knee/physiopathology , Pain Measurement , Pain, Postoperative/etiology , Range of Motion, Articular , Reoperation/statistics & numerical data , Walking/physiology
13.
Scand J Urol Nephrol ; 36(3): 228-30, 2002.
Article in English | MEDLINE | ID: mdl-12201942

ABSTRACT

We report a case of renal cell carcinoma (chromophobe type) in a female in the first trimester of her first pregnancy. The tumour was removed completely. Postoperatively single live pregnancy was confirmed and subsequently resulted in spontaneous vaginal delivery at term of a healthy infant.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Pregnancy Complications, Neoplastic , Adult , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Female , Humans , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/pathology , Pregnancy Complications, Neoplastic/surgery , Pregnancy Trimester, First
14.
J Egypt Soc Parasitol ; 31(3): 725-36, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11775099

ABSTRACT

Human fascioliasis is increasing in the Nile Delta particularly in Dakahlia Governorate, where it reached 7.47%. In this study, the tetrad of fascioliasis was established as high eosinophilia (100%), fever (85.6%), painful hepatomegaly (81.93%) and anaemia (100%). The laboratory results showed ESR accelerated in 87%, ALT elevated in 21.5%, AST elevated in 21.9%, S. bilirubin elevated in 16.5%, gamma GT elevated in 80.6%, and SAP elevated in 76.4%. Abdominal ultrasonography showed variable findings, as hepatomegaly, splenomegaly, periportal fibrosis, thickened wall of gall bladder, dilated common bile duct, dilated biliary radicals (partial), dilated common bile duct and biliary radicals (total), Fasciola worms in gall bladder, Fasciola worms in common bile duct, stones in gall bladder, stones in bile duct, cystic lesions in the liver, local lesions in the liver and ascitis. The highest was hepatomegaly in 81.93% of fascioliasis patients and the lowest was biliary dilated radicles (partial) in 0.26%.


Subject(s)
Fascioliasis/epidemiology , Abdomen/diagnostic imaging , Egypt/epidemiology , Fascioliasis/physiopathology , Female , Health Surveys , Humans , Liver Function Tests , Male , Prevalence , Ultrasonography
17.
Boll Chim Farm ; 137(5): 157-64, 1998 May.
Article in English | MEDLINE | ID: mdl-9689902

ABSTRACT

Our study was done to assess the value of administration of vitamin D to tuberculous children. The study included twenty four newly diagnosed tuberculous children; eleven males and thirteen females. Their age ranged from one and half to thirteen years. Thirteen patients were extra thoracic type of T.B., while only seven were intrathoracic and the rest were mixed. They were randomly divided into two Groups according to the treatment administered: Group A patients were given Rifampicin, Isoniazid and Streptomycin. Group B received in addition vitamin D. After eight weeks therapy, the patients of each group were evaluated regarding clinical, laboratory, and radiological improvement. Vitamin D level is raised after treatment in both Groups A and B, but this rise is not significant. It also showed insignificant difference between the two groups. Vitamin D level showed very high significant decrease in tuberculous children than matched healthy controls (non tuberculous children). Calcium was significantly elevated after treatment in Group A whereas no significant change was detected in Group B. Phosphorous was highly significantly elevated after treatment in Group A, whereas in Group B it is just significantly elevated. Alkaline phosphatase level in both groups A and B were slightly decreased after treatment. However, this decrease was not significant. Clinical improvement was more evident in Group B patients (those taking vitamin D) as compared to Group A patients. The same was noted with X-ray and Sonographic findings. We concluded that vitamin D therapy may be of great value in addition to antituberculous drugs in the treatment of tuberculous children, and its use is highly recommended.


Subject(s)
Tuberculosis/drug therapy , Vitamin D/therapeutic use , Adolescent , Body Weight , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Infant , Male
18.
Cancer Res ; 57(21): 4811-6, 1997 Nov 01.
Article in English | MEDLINE | ID: mdl-9354443

ABSTRACT

pH-mediated conversions in the structure of the topoisomerase (topo) I inhibitors camptothecin (CPT) and its analogues have strong implications for the pharmacokinetics and pharmacodynamics of these novel anticancer agents. Because the cell-penetrating and biologically active lactone isomers predominate at acidic conditions, we have tested if low pH potentiates the cytotoxic and antitumor effects of CPT and its water-soluble derivative topotecan (TPT). In L1210 leukemia cells, rapid initial uptake of radiolabeled CPT and TPT was followed by a gradual release from cells at physiological pH 7.4, whereas high drug levels were maintained in cells at pH 6.2. Steady-state uptake levels of CPT increased proportionally, up to 5-fold, with decreasing pH of the incubating medium (from 7.4 to 6.0). With TPT, a maximum 3-fold increase was observed at pH 6.8 to 6.4. By contrast, the cellular pharmacokinetics of the topoisomerase II inhibitor etoposide (ETP) were independent of the ambient pH. The large increases in intracellular CPT and TPT levels caused only moderate potentiation of cytotoxicity in short-term incubations. Conditions of very low pH < or =6.2 even antagonized the cytotoxicity of the topo I and topo II inhibitors, due to inhibition of DNA synthesis by intracellular acidification. However, in clinically relevant schedules of prolonged exposures at low drug concentration, low pH potentiated the cytotoxicity of CPT and TPT by 2-3-fold. To investigate the effect of local pH in vivo, the basal interstitial pH of 6.8 of RIF-1 tumors was selectively lowered by i.p. injection of the host animals with the mitochondrial inhibitor meta-iodobenzylguanidine (32 mg/kg) and glucose (1.5 g/kg). In accordance with the pH optimum for TPT uptake at pH 6.8 to 6.4, tumor acidification had no effect on the antitumor effect of this analogue. By contrast, the intervention significantly potentiated the response of tumors to CPT. The results indicate that local pH is an important determinant of the cellular pharmacokinetics and the antitumor activity of CPT and analogues.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Camptothecin/pharmacokinetics , Leukemia L1210/metabolism , Topotecan/pharmacokinetics , Animals , Antineoplastic Agents/pharmacology , Camptothecin/pharmacology , DNA, Neoplasm/biosynthesis , Hydrogen-Ion Concentration , Leukemia L1210/drug therapy , Mice , Mice, Inbred C3H , Topotecan/pharmacology
19.
Talanta ; 43(9): 1511-8, 1996 Sep.
Article in English | MEDLINE | ID: mdl-18966630

ABSTRACT

The effects of different organic solvent-water mixtures on the acidity constants of some azomethines derived from 3-amino-1,2,4-triazol; 2-amino-1,3-pyrimidine and also 2-amino-4-methyl-1,3-pyrimidine have been examined. Two pK(a) values for the o-OH derivatives were determined; one is assigned to the deprotonation of the nitrogen azomethine group and the other one is ascribed to the ionization of the OH group. The p-OH derivatives give one K(a) due to the ionization of the OH group. On the other hand, it was observed that with the increase in the amount of organic solvent in the medium, the pK(a) of the compound studied is decreased. This behaviour can be accounted for in terms of the high stabilization of both the non-protonated and ionic forms of these compounds by dispersion forces rather than by hydrogen bonding. Also, the effects of medium polarizability on the K(a) values and thus on the spectra of the charge transfer band observed have been discussed.

20.
Soc Sci Med ; 36(8): 1063-9, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8475422

ABSTRACT

Maternal beliefs and perceptions about breastfeeding and weaning were investigated in a series of in-depth, open-ended interviews with 20 mothers of infants aged 2-12 months in a poor neighborhood of metropolitan Cairo during July-September 1990. The traditional pattern of breastfeeding well into or through the second year of life is changing rapidly, although essentially all mothers still wish to breastfeed and do so at least initially. Beliefs and behaviors reported varied somewhat by rural/urban origins of the mother herself, but exhibited consensus on many issues. The ability to breastfeed successfully is perceived to be a blessing, and to require maturity, patience and a sense of responsibility. The quantity and quality of breast milk are believed to be influenced by a wide variety of factors including the childs age and individual characteristics, the psychological and physical state of the mother, and her diet. Mothers reported a number of behaviors that are perceived to influence the quality of breast milk including changes in their diet when the infant was ill and behaviors designed to optimize the humoral qualities (hot/cold, light/heavy) of the milk. Supplementation with sugar water beings very early, and gradual introduction of other foods generally is begun soon after 40 days of age. Mixed formula and breastfeeding is commonly perceived to increase the nutritional quality of the childs diet. Weaning is ideally related to developmental milestones (walking, complete dentition) but often occurs early due to a variety of factors including maternal illness, desire for another pregnancy, and perceptions that breast milk may be inadequate. Weaning is perceived to be a difficult and dangerous transition.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Breast Feeding , Health Knowledge, Attitudes, Practice , Urban Population , Weaning , Adult , Age Factors , Breast Feeding/psychology , Egypt , Female , Humans , Infant , Infant Food , Male , Poverty
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