Promising applications of cold plasma for microbial safety, chemical decontamination and quality enhancement in fruits.

Consumers' demand is increasing for safe foods without impairing the phytochemical and sensory quality. In turn, it has increased research interest in the exploration of innovative food processing technologies. Cold plasma technology is getting popularity now days owing to its high efficacy in decontamination of microbes in fruit and fruit-based products. As a on-thermal approach, plasma processing maintains the quality of fruits and minimizes the thermal effects on nutritional properties. Cold plasma is also exploited for inactivating enzymes and degrading pesticides as both are directly related with quality loss and presently are most important concerns in fresh produce industry. The present review covers the influence of cold plasma technology on reducing microbial risks and enhancing the quality attributes in fruits.

Primary hyperparathyroidism and pancreatitis.

PURPOSE: The true association between primary hyperparathyroidism (PHPT) and pancreatitis continues to be controversial. In this study, we present clinical data, investigative profile, management and follow-up of PHPT patients with pancreatitis and compare this group with PHPT patients without pancreatitis. METHODS: Records of 242 patients with PHPT managed at our center over 24 years were retrospectively analyzed for demographic and laboratory data. The diagnosis of pancreatitis was entertained in the presence of at least two of the three following features: abdominal pain, levels of serum amylase greater than three times the normal or characteristic features at imaging. RESULTS: Fifteen (6.19%) of the 242 consecutive patients with PHPT had had pancreatitis. Fourteen patients (93.3%) had acute pancreatitis (AP), while one patient had chronic calcific pancreatitis. Over half (8 of 14) of the patients with AP had at least two episodes of pancreatitis. Pancreatitis was the presenting symptom in 14 (93.3%) patients. None of the pancreatitis cases had additional risk factors for pancreatitis. PHPT patients with pancreatitis had significantly higher serum calcium and ALP than PHPT patients without pancreatitis. After successful parathyroidectomy, 14 patients had no further attacks of pancreatitis during a median follow-up of 16 months (range 2-41 months), while recurrence of pancreatitis was seen in one patient. CONCLUSIONS: We conclude that pancreatitis can be the only presenting complaint of PHPT. Our study highlights the importance of fully investigating for PHPT in any pancreatitis patient with high normal or raised serum calcium level, especially in the absence of other common causes of pancreatitis.

HbA1c measurement and relationship to incident stroke.

AIMS: To determine the proportion of people with diabetes who have HbA1c measured, what proportion achieve an HbA1c level of < 58 mmol/mol (7.5%), the frequency of testing and if there was any change in HbA1c level in the year before and the year after an incident stroke. METHODS: This study used the Secure Anonymised Information Linkage (SAIL) databank, which stores hospital data for the whole of Wales and ~ 65% of Welsh general practice records, to identify cases of stroke in patients with diabetes between 2000 and 2010. These were matched against patients with diabetes but without stroke disease. We assessed the frequency of HbA1c testing and change in HbA1c in the first year after stroke. Estimation was made of the proportion of patients achieving an HbA1c measurement ≤ 58 mmol/mol (7.5%). RESULTS: There were 1741 patients with diabetes and stroke. Of these, 1173 (67.4%) had their HbA1c checked before their stroke and 1137 (65.3%) after their stroke. In the control group of 16 838 patients with diabetes but no stroke, 8413 (49.9%) and 9288 (55.1%) had their HbA1c checked before and after the case-matched stroke date, respectively. In patients with diabetes and stroke, HbA1c fell from 61-56 mmol/mol (7.7-7.3%) after their stroke (P < 0.001). Before the study, 55.0% of patients with stroke had an HbA1c ≥ 58 mmol/mol compared with 65.2% of control patients, these figures were 62.5% and 65.3% after the stroke. CONCLUSIONS: The frequency of diabetes testing was higher in patients who had experienced a stroke before and after their incident stroke compared with control patients but did not increase after their stroke. Glucose control improved significantly in the year after a stroke.

An experience of ultrasound-guided hydrostatic reduction of intrussusception at a tertiary care centre.

BACKGROUND: Intussusception is an important and one of the most commonly encountered diagnoses of intestinal obstruction in the paediatric age group. Ultrasound-guided hydrostatic reduction is an effective, nonoperative treatment modality for this condition and is associated with a high success rate. In addition, it is simple and safe as the entire procedure is carried out with real-time ultrasound, without the hazard of radiation. The aim of this study was to evaluate the effi cacy and safety of ultrasound-guided hydrostatic reduction in the management of intussusceptions in the paediatric age group. METHOD: A case study was carried out on 89 patients diagnosed with intussusception using high-resolution ultrasonography over a period of two years, spanning February 2012 to January 2014. Ultrasound-guided hydrostatic reduction was performed in 78 of these patients, and 11 patients were excluded owing to clinical contraindications. Follow-up ultrasound was performed after 24 hours to rule out recurrence. RESULTS: The disease was most prevalent in the age group 6-24 months. The ileocolic type was the most common. Mean duration (hours) was 17.02 ± 20.81 for time to presentation. Complete therapeutic reduction was achieved in 70 of the 78 cases, with a success rate of 90%. Two recurrences occurred in the following 24 hours, which were successfully reduced on the second attempt. Complications and mortality did not occur secondary to the procedure. CONCLUSION: Our study found that ultrasound-guided hydrostatic reduction is a simple, safe and effective nonoperative treatment for intussusceptions in the paediatric age group, and should be the fi rst line of management in appropriate patients.

Metal Strip Implanted Tunneling Field-Effect Transistor Biosensor as a Label-Free Biosensor.

In this study, we design and simulate a metal implanted dielectrically modulated tunneling field-effect transistor (MI-DMTFET). In the ambipolar conduction state, the proposed structure works as an efficient sensor for the detection of a wide range of biomolecules. A metal strip (MS) is implanted above the drain-channel junction in the gate dielectric to improve the alignment of band gaps. Therefore, with the help of implanted metal work function engineering, the tunneling barrier gets lowered, which in turn increases the ambipolar current. An optimum metal-strip implant work function of 4.85 eV and a length of 1.5 nm have resulted in significantly improved performance of the proposed device. It has been observed that when the biomolecules with varying dielectric constants and charge densities are captured in the nanogap cavity, the ambipolar current of the biosensor changes, resulting in the detection of the biomolecules. Quantitative and comprehensive analyses of device parameters such as surface potential, electric field, band-to-band tunneling, subthreshold slope, and ION/IOFF ratio analysis have been performed. Rigorous comparative analyses of key performance-measuring parameters have been performed with a conventional sensor device. It has been found that the proposed device offers maximum sensitivity of 1220 under an ambipolar state at k = 12.

Deceased donor renal transplantation at army hospital research and referral: Our experience.

CONTEXT: In India, there are a large number of end-stage renal disease (ESRD) patients waiting for renal transplant. Deceased donor organ transplantation (DDOT) is the possible solution to bridge the disparity between organ supply and demand. The concept of expanded criteria donors (ECDs) was developed to combat the huge discrepancy between demand and organ availability. However, ECD kidneys have a higher propensity for delayed graft function (DGF), and therefore worse long-term survival. We present our experience of deceased donor renal transplantation. AIMS: We report single centre experience on DDOT including ECDs vis-à-vis patient/graft survival, graft function in terms of serum creatinine (SCr), rejection episodes, and delayed graft function in 44 DDOT. MATERIALS AND METHODS: Between August 1998 and April 2011, 44 renal transplants from 35 deceased donors were performed, of which 37.2% were expanded criteria donors. Results were analyzed in terms of age of donor, terminal SCr, graft ischemia time, graft function, post-transplant complications, and graft and patient survival. All recipients received sequential triple drug immunosuppression and induction with rabbit antithymocyte globulin (rATG). The induction is commenced by giving first dose of rATG intraoperatively (dose 1.5 mg/kg) and subsequent rATG infusions were administered daily for a minimum of 5 and maximum of 7 doses depending on initial graft function. RESULTS: We have been able to achieve a mean cold ischemia time of 6.25 ± 2.55 h due to the coordinated team efforts. Delayed graft function occurred in 34% patients and 31.8% had prolonged drainage. There were no urinary leaks. Seven (16%) patients had biopsy-proven rejection episodes, all of which were reversed with treatment. Two patients underwent graft nephrectomy. One of these was due to hyperacute rejection and another due to anastomotic hemorrhage. One-year graft survival was 92.4% and the patient survival was 83.8%. CONCLUSION: Deceased donor renal transplants have satisfactory graft function and patient survival despite the high incidence of delayed graft function. Retrieving kidneys from marginal donors can add to the donor pool.

RiRPSSP: A unified deep learning method for prediction of regular and irregular protein secondary structures.

Protein secondary structure prediction (PSSP) is an important and challenging task in protein bioinformatics. Protein secondary structures (SSs) are categorized in regular and irregular structure classes. Regular SSs, representing nearly 50% of amino acids consist of helices and sheets, whereas the remaining amino acids represent irregular SSs. [Formula: see text]-turns and [Formula: see text]-turns are the most abundant irregular SSs present in proteins. Existing methods are well developed for separate prediction of regular and irregular SSs. However, for more comprehensive PSSP, it is essential to develop a uniform model to predict all types of SSs simultaneously. In this work, using a novel dataset comprising dictionary of secondary structure of protein (DSSP)-based SSs and PROMOTIF-based [Formula: see text]-turns and [Formula: see text]-turns, we propose a unified deep learning model consisting of convolutional neural networks (CNNs) and long short-term memory networks (LSTMs) for simultaneous prediction of regular and irregular SSs. To the best of our knowledge, this is the first study in PSSP covering both regular and irregular structures. The protein sequences in our constructed datasets, RiR6069 and RiR513, have been borrowed from benchmark CB6133 and CB513 datasets, respectively. The results are indicative of increased PSSP accuracy.

Weighted ensemble model for image classification.

The Deep Convolutional Neural Network (DCNN) classification models are being tremendously used across many research fields including medical science for image classification. The accuracy of the model and reliability on the results of the model are the key attributes which determine whether a particular model should be used for a specific application or not. A highly accurate model is always desirable for all applications of machine learning as well as deep learning. This paper presents a DCNN based heterogeneous ensemble approach where all DCNN models can be trained on a single dataset and each model can contribute of towards the final output of the ensemble model. The contribution of each model is weighted according to its individual accuracy on the given dataset. Models with higher accuracy has higher contribution in the final output of ensemble model, whereas the models with lower accuracy has lower contribution. This approach, when tested on two different X-ray images datasets of Covid-19, has confirmed the significant increase in 3-class accuracy as compared to the models in literature.

Nanotechnology future in food using carbohydrate macromolecules: A state-of-the-art review.

It is commonly known that agricultural pest and disease management is achieved through the use of agricultural chemicals and other synthetic compounds, which can contaminate water, soil, and food. Using agrochemicals indiscriminately has negative effects on the environment and poor food quality. In contrast, the world's population is increasing rapidly, and arable land is diminishing daily. Traditional agricultural methods must be replaced by nanotechnology-based treatments that efficiently address both the demands of the present and the needs of the future. As a promising contributor to sustainable agriculture and food production worldwide, nanotechnology has been applied through innovative and resourceful tools. Recent advances in nanomaterial engineering have increased agricultural and food sector production and protected crops using nanoparticles (1000 nm). Agrochemicals, nutrients, and genes can now be distributed to plants in a precise and tailored manner through nanoencapsulation (nanofertilizers, nanopesticides, and genes). Despite the advancement of technology in agriculture, some areas remain unexplored. The various agricultural domains must therefore be updated in priority order. The development of long-lasting and efficient nanoparticle materials will be key to the development of future eco-friendly and nanoparticle-based technologies. We thoroughly covered the many types of nanoscale agro-materials and gave an overview of biological techniques in nano-enabled tactics that can effectively reduce plant biotic and abiotic challenges while potentially boosting plant nutritional values.

Faceted Antimony Particles with Interiors Reinforced with Reduced Graphene Oxide as High-Performance Anode Material for Sodium-Ion Batteries.

The attainment of "true reinforcement" in a composite and harnessing of the associated beneficial effects have been demonstrated here through the development of faceted crystalline Sb particles having the interiors reinforced with reduced graphene oxide (rGO). Such a unique and "near-ideal" micro/nanocomposite architecture has been achieved via a facile/cost-effective route by facilitating heterogeneous nucleation/growth of Sb-oxide particles on/around dispersed rGO sheets upon incorporation of the same directly into the precursor suspension, followed by the reduction of Sb-oxide to Sb, in intimate contact with the rGO, during the subsequent single heat-treatment step. As a potential anode material for Na-ion batteries, the as-developed Sb/rGO composite exhibits a reversible Na-storage capacity of ∼550 mAh/g (@ 0.2 A/g) and a fairly high first cycle Coulombic efficiency (CE) of ∼79%, with the good reversibility being attributed to the coarse particle size of Sb and encompassing of rGO sheets inside the Sb particles. Furthermore, despite the coarse particle size, the Sb/rGO-based electrode exhibits outstanding cyclic stability, with negligible capacity fade up to 150 cycles (viz., ∼97% capacity retention), and rate capability, with >86% capacity being obtained upon raising the current density from 0.1 to 2 A/g, resulting in a capacity of ∼490 mAh/g, even at 2 A/g.

Morpho-Cultural and Pathogenic Variability of Sclerotinia sclerotiorum Causing White Mold of Common Beans in Temperate Climate.

The present systematic research on cultural, morphological, and pathogenic variability was carried out on eighty isolates of Sclerotinia sclerotiorum collected from major common bean production belts of North Kashmir. The isolates were found to vary in both cultural and morphological characteristics such as colony color and type, colony diameter, number of days for sclerotia initiation, sclerotia number per plate, sclerotial weight, and size. The colony color ranged between white and off-white with the majority. The colony was of three types, in majority smooth, some fluffy, and a few fluffy-at-center-only. Colony diameter ranged between 15.33 mm and 29 mm after 24 h of incubation. The isolates took 4 to 7 days for initiation of sclerotia and varied in size, weight, and number per plate ranging between 14 and 51.3. The sclerotial arrangement pattern on plates was peripheral, sub peripheral, peripheral, and subperipheral, arranged at the rim and scattered. A total of 22 Mycelial compatibility groups (MCGs) were formed with seven groups constituted by a single isolate. The isolates within MCGs were mostly at par with each other. The six isolates representing six MCGs showed variability in pathogenicity with isolate G04 as the most and B01 as the least virulent. The colony diameter and disease scores were positively correlated. Sclerotia were observed to germinate both myceliogenically and carpogenically under natural temperate conditions of Kashmir. Germplasm screening revealed a single resistant line and eleven partially resistant lines against most virulent isolates.

Presentation and clinical course of Wolfram (DIDMOAD) syndrome from North India.

AIMS: Wolfram syndrome, also known as DIDMOAD, is a relatively rare inherited neurodegenerative disorder, first evident in childhood as an association of juvenile-onset diabetes mellitus and optic atrophy, followed by diabetes insipidus and deafness. The aim of the study was to examine the clinical profile of patients with DIDMOAD syndrome presenting to a tertiary care hospital in north India. METHODS: Clinical presentation of juvenile-onset diabetes mellitus fulfilling the diagnosis of Wolfram syndrome was studied using a prepared standardized form. RESULTS: Subjects with juvenile-onset non-autoimmune diabetes mellitus attending the diabetic clinic at a tertiary care centre in north India were followed for 10 years and a diagnosis of fully developed Wolfram syndrome was confirmed in seven individuals. The series consisted of five male and two female patients with a mean age of 17.5 ±7.34 years. Two subjects had consanguinity and none had any other family member affected. Optic atrophy was present in all, sensorineural hearing loss in 4/7, central diabetes insipidus in 4/7 and nephrogenic diabetes insipidus in 2/7 subjects. The new associations found were: spastic myoclonus, short stature with pancreatic malabsorption, nephrogenic diabetes insipidus, cyanotic heart disease and choledocholithiasis with cholangitis. Genetic analysis revealed mutation in exon 8 of the WFS1 gene in all the cases studied. CONCLUSIONS: The present clinical series of Wolfram syndrome reveals a varied clinical presentation of the syndrome and some new associations.

Head injury caused by tear gas cartridge in teenage population.

OBJECTIVES: The aim of this study was to assess the head injury in children caused by an unusual projectile, a tear gas cartridge. The study is the only one on this subject which has been done in a teenage population. METHOD: This was a prospective study conducted over a period of 4 years in which all the patients aged less than or equal to 18 years and who had a head injury due to a tear gas cartridge were included. RESULTS: We had 5 patients in our study group. All the patients were males. Commonest CT scan finding was brain contusion with skull fracture. One of our patients died. One patient continues to be in vegetative state whereas 3 had a good outcome. CONCLUSION: Tear gas cartridge, though considered as one of the benign modalities of controlling agitated crowds, is not really benign. It can cause serious injuries and mortality. The personnel using them might be trained in a better way so that the people do not receive direct hits. In addition some changes in the design of tear gas cartridge can be done to decrease the impact to the skull.

DNA topoisomerase I--targeted chemotherapy of human colon cancer in xenografts.

Drug development is needed to improve chemotherapy of patients with locally advanced or metastatic colon carcinoma, who otherwise have an unfavorable prognosis. DNA topoisomerase I, a nuclear enzyme important for solving topological problems arising during DNA replication and for other cellular functions, has been identified as a principal target of a plant alkaloid 20(S)-camptothecin. Significantly increased concentrations of this enzyme, compared to that in normal colonic mucosa, were found in advanced stages of human colon adenocarcinoma and in xenografts of colon cancer carried by immunodeficient mice. Several synthetic analogs of camptothecin, selected by tests with the purified enzyme and tissue-culture screens, were evaluated in the xenograft model. Unlike other anticancer drugs tested, 20(RS)-9-amino-camptothecin (9-AC) induced disease-free remissions. The overall drug toxicity was low and allowed for repeated courses of treatment.

Postpartum Acute Kidney Injury: Experience of a Tertiary Care Center.

Pregnancy-related-acute kidney injury (PR-AKI) had decreased from 40% to 20% in 1960 to <10% in recent series, mostly due to meticulous antenatal management. Postpartum-AKI (PP-AKI) resulting from late obstetric complications has become more apparent after improvement in antenatal care and legalization of medical termination of pregnancy. Women with renal injury in peripartum period admitted to our hospital over a period of 2 years (April 2013 to May 2015) were studied. Of 713 patients of AKI admitted, 61 had PR-AKI with an incidence of 4.27%. Out of the 61 patients, 28 had PP-AKI with an incidence of 1.96%. The mean age of patients with PP-AKI was 26.10 ± 4.3 years. Sepsis was the most common cause accounting for 11 (39.28%) cases followed by postpartum hemorrhage (PPH) in 7 (25%) cases. Renal biopsy was done in nine patients, out of whom four were having cortical necrosis. Patients having diffuse cortical necrosis remained dialysis-dependent. High contribution of sepsis and PPH to PP-AKI in our setting makes it an ideal target for rectification. Protocolized peripartum monitoring and standard clinical practices of asepsis will go long way in decreasing the incidence of PP-AKI and maternal morbidity in our valley.

Cytopathology of the central nervous system. Part I. Utility of crush smear cytology in intraoperative diagnosis of central nervous system lesions.

OBJECTIVE: To evaluate the utility of rapid intraoperative crush smear cytologic diagnosis of central and peripheral nervous system lesions and to determine the accuracy and relevance of the accuracy of the intraoperative cytologic diagnosis when compared to the final paraffin section diagnosis. STUDY DESIGN: The crush (squash) smear technique was introduced at Sher-i-Kashmir Institute of Medical Sciences in May 2003. The 8 months of 2003 were used for standardization of the procedure. In 2004, 151 patients with open neurosurgical specimens or stereotactic biopsies were diagnosed intraoperatively by crush smears, and the diagnosis was compared with final diagnosis on paraffin sections of the same tissue samples. No supplementation of frozen sections was used. RESULTS: Of 151 cases, 144 were diagnosed accurately intraoperatively by crush smear cytology when compared with the respective paraffin section diagnoses. The diagnostic accuracy attained was 95.36%. Each case was diagnosed within 10 minutes after receipt of sample. Neurosurgical procedure (open or stereotaxy) did not affect diagnostic accuracy. CONCLUSION: In the expert hands of a pathologist with good exposure neurosurgical specimens, crush smear cytology is an accura and reliable procedure for the intraoperative diagnosis central nervous system tumors.

Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture.

Camptothecin and taxol are secondary metabolites found, respectively, in the wood bark of Camptotheca acuminata, a native of China, and Taxus brevifolia, found in the northwest Pacific coastal region of the United States. The compounds were isolated guided by bioassay on various extracts and chromatographic fractions. Their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry, and X-ray analysis. Both compounds have unique mechanisms of antitumor activity; camptothecin uniquely inhibits an enzyme, topoisomerase I, involved in DNA replication. Taxol binds to a protein, tubulin, thus inhibiting cell division. Taxol has been called the best new anticancer agent developed from natural products, showing particular efficacy against ovarian cancer. Camptothecin and analogues singly or combined with cisplatin show efficacy against solid tumors, breast, lung, and colorectal, which hitherto have been unaffected by most cancer chemotherapeutic agents.

Increased methotrexate resistance and dhfr gene amplification as a consequence of induced Ha-ras expression in NIH 3T3 cells.

Oncogene activation and loss of tumor suppressor genes are known to play a role in tumor initiation as well as its progression. The potential roles of these genes in perturbation of genome stability has become a major interest. To better understand the relationship between expression of an oncogene and genetic instability, we have studied a cell line expressing an activated human Ha-ras under the control of bacterial lactose operon regulatory elements for changes in methotrexate resistance and dihydrofolate reductase (dhfr) gene amplification following mutant Ha-ras induction. In these cells mutant Ha-ras is directed by an inducible SV40 promoter containing a bacterial lac operator sequence which is repressed due to constitutive expression of bacterial lac repressor gene. The expression of this Ha-ras is specifically induced by the addition of isopropyl-1-thio-beta-D-galactopyranoside (IPTG), a lactose analogue, to the culture medium. During single-step methotrexate selection, these cells showed an increased frequency of methotrexate resistance in the presence of IPTG. More than 60% of the methotrexate-resistant colonies showed a 2-6-fold amplification of the dhfr gene. One clone with rearranged dhfr had about 100-fold amplification of the gene. The increased capacity to amplify DNA in response to mutant Ha-ras induction was not locus specific since cells also displayed an increased frequency of resistance to N-(phosphonacetyl)-L-aspartic acid in the presence of ITPG. Four of the methotrexate-resistant clones with amplified dhfr gene were cultured further in the presence or absence of IPTG and subsequently compared for their ability to grow in soft agar as a measure of transformation. In medium containing methotrexate but no IPTG, the clones were unable to grow in soft agar, indicating that methotrexate resistance due to gene amplification is separable from transformation.

Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP-responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53.

The tumor suppressor protein p53 regulates various cellular responses to DNA damage and plays a significant role in DNA repair. The nuclear p300/cyclic AMP-responsive element binding (CREB)-binding protein (CBP) proteins act as coactivators in supporting the transcription function of p53. We examined the role of the human homologue of yeast Rad23 protein A (hHR23A), one of the two human homologues of the Saccharomyces cerevisiae nucleotide excision repair gene product Rad23, in the p300/CBP-associated regulation of p53 activity. Overexpression of wild-type hHR23A inhibits the p53 transcriptional activity and results in a decreased steady-state protein level of cellular p53. The inhibitory effect of hHR23A can be overcome by the concomitant expression of p300, CBP, and p300 segments harboring C/H1 domain and neutralized by the coexpression of HIV accessory protein Vpr, which binds COOH terminus of hHR23A/B. Additionally, hHR23A was shown to interact in vitro and in vivo with p300 segments harboring C/H1 domain. These studies provide evidence for the involvement of hHR23A in the regulation of p53 activity through p300/CBP. Although the precise direct role of hHR23 proteins in regulation of p53 and DNA repair remains to be elucidated, our data suggest that the interaction between hHR23A and p300/CBP has important implications in cross-talk between the p53 pathway and DNA repair.

Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells.

In order to understand the high efficacy of camptothecin derivatives against human colon tumor xenografts in nude mice, we have studied the transport properties of camptothecin derivatives across cellular membranes of MDR1-overexpressing cells. MDR1 overexpression was shown to have little effect on camptothecin cytotoxicity; camptothecin was equally cytotoxic to both the drug-sensitive parental cell line, KB 3-1, and its multidrug-resistant derivative, KB V1. The ability of camptothecin to overcome MDR1-mediated resistance is most likely due to unimpaired accumulation of camptothecin in MDR1 cells as suggested from the following experiments: (a) cytotoxicity of camptothecin against KB V1 cells was not altered by the known MDR1-reversing agent, verapamil; (b) camptothecin was ineffective as compared with vinblastine in competing with [3H]azidopine for photoaffinity labeling of MDR1; (c) camptothecin was equally efficient in trapping cellular topoisomerase I molecules on chromosomal DNA in the form of cleavable complexes in both KB 3-1 and KB V1 cells. The mechanism by which camptothecin overcomes MDR1-mediated resistance has been further studied using a number of uncharged and charged camptothecin derivatives. In contrast to the uncharged camptothecin derivatives, such as 9-amino-camptothecin and 10,11-methylenedioxy-camptothecin, the charged camptothecin derivative, topotecan, showed reduced cytotoxicity against MDR1-overexpressing KB V1 cells. The reduced cytotoxicity of topotecan in KB V1 cells was due to the overexpression of MDR1 in KB V1 cells since verapamil restored both topotecan accumulation and cytotoxicity. These results suggest that the charge on camptothecin can affect the drug's sensitivity to MDR1. The possible effect of membrane permeability in determining drug selectivity of MDR1 is discussed.