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1.
JNMA J Nepal Med Assoc ; 61(259): 220-223, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37203960

ABSTRACT

Introduction: Early canities are the premature greying of hair before the age of 25 years in Asians. The condition is a matter of concern for young adults aesthetically. This study aimed to find out the prevalence of early canities among undergraduate medical students of a medical college. Methods: A descriptive cross-sectional study was carried out from 1 December 2021 to 30 June 2022 among undergraduate medical students at a medical college. The study was conducted after receiving ethical approval from the Institutional Review Committee [Reference number: 146(6-11)C-2 078/079]. The participants with ages less than 25 years without a history of vitiligo, intake of chemotherapeutic drugs, progeria, pangeria and recent dyeing of hair were enrolled. A convenience sampling method was used. Point estimate and 95% Confidence Interval were calculated. Results: Out of 235 students, 95 (40.42%) (34.15-46.69, 95% Confidence Interval) had early canities. The most prevalent premature greying was grade I early canities i.e.79 (83.15%) of participants. Among the participants with early canities, 56 (58.94%) were male, 41 (43.15%) had a positive family history for early canities, 67 (70.52%) had normal body mass index and 38 (40%) had O+ve blood group. Conclusions: The prevalence of early canities among undergraduate medical students was lower than in other studies done in similar settings. The grade I early canities was seen more among the participants with premature greying of hair. Keywords: epidemiology; hair colour; medical students; physiology.


Subject(s)
Students, Medical , Young Adult , Male , Humans , Adult , Female , Cross-Sectional Studies , Hair , Coloring Agents , Research Design
2.
J Nepal Health Res Counc ; 21(2): 309-312, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38196226

ABSTRACT

BACKGROUND: Spirometry is the most common pulmonary function tests that specifically measures volume and flow of air during respiration. It helps to identify obstructive and restrictive diseases of the lungs. The alterations of the results in spirometry can happen even in normal health due to change in body postures that alter lung volumes and muscle biomechanics. So, the objective of this study is to determine the effects of change of postures mainly supine, sitting and standing on pulmonary parameters of young healthy volunteers. METHODS: A cross-sectional analytical study was conducted among young medical students of Maharajgunj Medical Campus in the department of Clinical Physiology. A total of 31 students were selected by convenient sampling technique. Pulmonary parameters: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1st second (FEV1), FEV1/FVC, Peak Expiratory Flow(PEF), EF2575 were collected from spirometry. The spirometry was done in supine, sitting and standing postures and the best value of each posture was selected for the comparison and obtained data were analyzed using repeated measures ANOVA with confidence interval of 95%. RESULTS: The pulmonary parameters recorded in different postures showed that the mean of these variables comparatively increased in standing posture than others with mean FVC 3.98±0.66 L, mean FEV1 3.53±0.55L, mean FEV1/FVC 89.23±5.60%, mean PEF 8.60±1.62L/s and mean PEF2575 4.46±1.08 L/s. The mean comparisons of these pulmonary parameters in supine, sitting and standing postures showed statistically significant differences with P value < 0.05. CONCLUSIONS: The pulmonary parameters are affected by body postures. Those parameters are recorded highest during standing posture and lowest during supine posture.


Subject(s)
Posture , Students, Medical , Humans , Cross-Sectional Studies , Healthy Volunteers , Nepal , Spirometry
3.
JNMA J Nepal Med Assoc ; 61(267): 840-843, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-38289744

ABSTRACT

Introduction: Pre-eclampsia is a pregnancy-related hypertensive disorder with maternal and neonatal complications. Many studies are done regarding the prevalence of pre-eclampsia in Nepal but ascertaining the maternal risk factors and fetal outcomes are important. The aim of this study was to find out the prevalence of pre-eclampsia among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among pregnant women admitted to the Department of Obstetrics and Gynaecology of a tertiary care hospital from 13 July 2023 to 29 September 2023 after obtaining ethical approval from the Institutional Review Committee. Convenience sampling method was used. Point estimate was calculated at a 95% Confidence Interval. Results: Among 5065 patient, pre-eclampsia was seen in 44 (0.87%) (0.61-1.13, 95% Confidence Interval). A total of 16 (36.36%) cases of pre-eclampsia were in the age group 25-29 years and 30 (68.18%) of them were nulliparous. A total of 38 (86.36%) of the newborns of the pre-eclamptic cases had low birth weight. The APGAR score of newborns at the 1 minute after birth was 26 (59.09%) followed by the newborns who needed re-evaluation 16 (36.36%). The APGAR score recorded at 5 minutes showed maximum newborns with normal APGAR score 40 (90.90%). Conclusions: The prevalence of pre-eclampsia among pregnant women was found to be lower than other studies done in similar settings. Keywords: maternity; Nepal; pre-eclampsia; prevalence.


Subject(s)
Gynecology , Pre-Eclampsia , Pregnancy , Female , Infant, Newborn , Humans , Adult , Pre-Eclampsia/epidemiology , Pregnant Women , Tertiary Care Centers , Cross-Sectional Studies
4.
J Nepal Health Res Counc ; 20(2): 494-498, 2022 Nov 03.
Article in English | MEDLINE | ID: mdl-36550734

ABSTRACT

BACKGROUND: The use of face masks has been associated with physiological changes in body. This study aims to know the changes in pulse rate and blood pressure components after wearing face masks during stairs climbing. METHODS: An experimental study was conducted among 60 apparently healthy young adults between 18-35 years of age. The pulse rate and blood pressure of the participants were recorded during rest at ground floor and after climbing the stairs till 5th floor at brisk and regular pace without wearing the face masks. The uniform KN95 masks were distributed and proper coverage of nose, mouth and chin were ensured. After 5 minutes interval, the pulse rate and blood pressure were recorded again at rest in ground floor and after climbing stairs with use of KN95 masks. RESULTS: At rest, the difference in mean pulse rate was statistically significant after wearing masks in participants between 21-25 years of age (86.46±14.59 bpm, p=0.014). After climbing the stairs, the mean pulse rate (131.16±18.48 bpm), mean systolic blood pressure (137.67±16.13 mmHg) and mean rate pressure product (182.87±41.70) were higher in participants (age group: 26-30 years) wearing masks and the difference was statistically significant (p=0.001; 0.013; 0.001respectively). During stairs climbing, the change in mean systolic blood pressure (32.66±16.73 mmHg), mean pulse pressure (43.77±24.64 mmHg) and mean rate pressure product (96.58±37.23) were higher in participants (age group: 26-30 years) and the difference was statistically significant (p=0.036; 0.047 and 0.009 respectively). CONCLUSIONS: The changes in systolic blood pressure, pulse pressure and rate pressure product are found to increase after wearing face masks during stairs climbing. It can be suggestive of increase workload to the heart by wearing face masks in addition to climbing the stairs.


Subject(s)
Masks , Young Adult , Humans , Adult , Blood Pressure , Heart Rate , Nepal
5.
Ann Neurosci ; 29(2-3): 159-165, 2022 Apr.
Article in English | MEDLINE | ID: mdl-36419523

ABSTRACT

Obsessive-compulsive disorder (OCD) is a disorder that is characterized by the presence of obsessions and compulsions. OCD can occur in a wide range of subtypes, which may include sexual OCD, i.e., the occurrence of intrusive sexual thoughts. People with sexual OCD may experience unwanted obsessive sexual thoughts about a family member, dead or inanimate objects, animals, God, or children, which can range from mild to severe levels of occurrence. The psychodynamic perspective on OCD suggests that the content of obsessive thinking is commonly drawn from primitivized sexuality and aggression. It further suggests that in the absence of key relationships that include emotional proximity, mirroring and containment, and attunement, a child experiences a void-like state. Consequently, the anxiety that arises in the child leads to a form of liveliness in a "dead" inner world. However, it occurs out of a sense of abandonment and loss of good objects, and ultimately out of fear of annihilation. As a result, the child resorts to maladaptive defense mechanisms. The study attempts to explore the adverse early childhood experiences such as parental neglect, mother-father conflict, and lack of parental love and care leading to fixation in psychosexual stages of development, which further leads to the adoption of maladaptive defense mechanisms that in turn further contribute to the development of obsessional personality traits. This study aims to explain the psychodynamic perspective on the emergence of sexual obsessions by proceeding with a case study approach by taking a diagnosed case of OCD. A comprehensive psychodiagnostic assessment was conducted with the help of Draw-a-Person Test, Thematic Apperception Test, Rotter's Incomplete Sentence Blank, and Million's Comprehensive Multiaxial Inventory. The analysis of the assessment protocol revealed a strong relationship between the defense mechanism, personality traits, and the development of obsessive symptoms.

6.
JNMA J Nepal Med Assoc ; 59(236): 342-345, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-34508526

ABSTRACT

INTRODUCTION: The upper and lower lip consists of the numerous amounts of fine grooves. This pattern of grooves will be definite throughout the lifetime. The groove of the lip shows variations and play important role in forensic medicine and crime investigation. The objective of this study is to find out the prevalence of type I lip print in at least one lip quadrant among first- and second- year medical and dental students of a medical college. METHODS: The study was conducted on 240 students of a medical college between November 2020- January 2021 after getting the ethical clearance from the Institutional Review Committee (reference no. KMC-IRC 0311202006). The convenient sampling was done. The patterns of the grooves of the lip were studied. The data was analysed with Statistical Package for the Social Sciences 20 version. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data. RESULTS: Out of 240 students, type I lip pattern was seen in at least one quadrant in 190 (79.6%) (73.38-84.94 at 95% CI) students. One hundred and fifty-nine (66.3%) had type I pattern in the right upper quadrant, 160 (66.7%) in left upper quadrant, 181 (75.4%) in right lower quadrant, and 177 (73.8%) in left lower quadrant. Type Ia was maximum found in 115 (47.9%) and type Ib in 66 (27.5%) in lower left quadrant of lip. CONCLUSIONS: Our findings showed a higher prevalence of type I lip pattern than those reported by other national studies done among medical students.


Subject(s)
Students, Dental , Students, Medical , Cross-Sectional Studies , Humans , Lip , Universities
7.
Int J Parasitol ; 49(13-14): 1061-1073, 2019 12.
Article in English | MEDLINE | ID: mdl-31733196

ABSTRACT

Meloidogyne incognita is a polyphagous plant-parasitic nematode that causes considerable yield loss in agricultural and horticultural crops. The management options available for M. incognita are extremely limited. Here we identified and characterised a M. incognita homolog of Caenorhabditis elegans sterol-binding protein (Mi-SBP-1), a transcriptional regulator of several lipogenesis pathway genes, and used RNA interference-mediated gene silencing to establish its utility as a target for the management of M. incognita. Mi-sbp-1 is predicted to be a helix-loop-helix domain containing DNA binding transcription factor, and is present in the M. incognita genome in three copies. The RNA-Seq analysis of Mi-sbp-1 silenced second stage juveniles confirmed the key role of this gene in lipogenesis regulation in M. incognita. In vitro and host-induced gene silencing of Mi-sbp-1 in M. incognita second stage juveniles resulted in loss of nematodes' ability to utilise the stored fat reserves, slower nematode development, and reduced parasitism on adzuki bean and tobacco plants. The multiplication factor for the Mi-sbp-1 silenced nematodes on adzuki bean plants was reduced by 51% compared with the control nematodes in which Mi-sbp-1 was not silenced. Transgenic expression of the double-stranded RNA construct of the Mi-sbp-1 gene in tobacco plants caused 40-45% reduction in M. incognita multiplication, 30-43.8% reduction in the number of egg masses, and 33-54% reduction in the number of eggs per egg mass compared with the wild type control plants. Our results confirm that Mi-sbp-1 is a key regulator of lipogenesis in M. incognita and suggest that it can be used as an effective target for its management. The findings of this study can be extended to develop methods to manage other economically important parasitic nematodes.


Subject(s)
Lipogenesis/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Tylenchoidea/enzymology , Tylenchoidea/metabolism , Animals , Caenorhabditis elegans Proteins/genetics , Gene Silencing , Plant Diseases/parasitology , Nicotiana/parasitology , Treatment Outcome , Tylenchoidea/growth & development , Vigna/parasitology
8.
Transgenic Res ; 28(3-4): 327-340, 2019 08.
Article in English | MEDLINE | ID: mdl-30955133

ABSTRACT

RNA interference (RNAi)-based host-induced gene silencing (HIGS) is emerging as a novel, efficient and target-specific tool to combat phytonematode infection in crop plants. Mi-msp-1, an effector gene expressed in the subventral pharyngeal gland cells of Meloidogyne incognita plays an important role in the parasitic process. Mi-msp-1 effector is conserved in few of the species of root-knot nematodes (RKNs) and does not share considerable homology with the other phytonematodes, thereby making it a suitable target for HIGS with minimal off-target effects. Six putative eggplant transformants harbouring a single copy RNAi transgene of Mi-msp-1 was generated. Stable expression of the transgene was detected in T1, T2 and T3 transgenic lines for which a detrimental effect on RKN penetration, development and reproduction was documented upon challenge infection with nematode juveniles. The post-parasitic nematode stages extracted from the transgenic plants showed long-term RNAi effect in terms of targeted downregulation of Mi-msp-1. These findings suggest that HIGS of Mi-msp-1 enhances nematode resistance in eggplant and protect the plant against RKN parasitism at very early stage.


Subject(s)
Gene Silencing , Helminth Proteins/antagonists & inhibitors , Merozoite Surface Protein 1/antagonists & inhibitors , Plant Diseases/immunology , Plants, Genetically Modified/immunology , Solanum melongena/immunology , Tylenchoidea/physiology , Amino Acid Sequence , Animals , Helminth Proteins/genetics , Host-Parasite Interactions/immunology , Merozoite Surface Protein 1/genetics , Plant Diseases/parasitology , Plant Roots/immunology , Plant Roots/parasitology , Plants, Genetically Modified/parasitology , Sequence Homology , Solanum melongena/parasitology
9.
Mol Plant Microbe Interact ; 32(7): 876-887, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30759351

ABSTRACT

Nematode chemosensation is a vital component of their host-seeking behavior. The globally important phytonematode Meloidogyne incognita perceives and responds (via sensory organs such as amphids and phasmids) differentially to various chemical cues emanating from the rhizosphere during the course of host finding. However, compared with the free-living worm Caenorhabditis elegans, the molecular intricacies behind the plant nematode chemotaxis are a yet-unexploited territory. In the present study, four putative chemosensory genes of M. incognita, namely, Mi-odr-1, Mi-odr-3, Mi-tax-2, and Mi-tax-4 were molecularly characterized. Mi-odr-1 mRNA was found to be expressed in the cell bodies of amphidial neurons and phasmids of M. incognita. Mi-odr-1, Mi-odr-3, Mi-tax-2, and Mi-tax-4 transcripts were highly expressed in early life stages of M. incognita, consistent with a role of these genes in host recognition. Functional characterization of Mi-odr-1, Mi-odr-3, Mi-tax-2, and Mi-tax-4 via RNA interference revealed behavioral defects in M. incognita and perturbed attraction to host roots in Pluronic gel medium. Knockdown of Mi-odr-1, Mi-odr-3, Mi-tax-2, and Mi-tax-4 resulted in defective chemotaxis of M. incognita to various volatile compounds (alcohol, ketone, aromatic compound, ester, thiazole, pyrazine), nonvolatiles of plant origin (carbohydrate, phytohormone, organic acid, amino acid, phenolic), and host root exudates in an agar-Pluronic gel-based assay plate. In addition, ascaroside-mediated signaling was impeded by downregulation of chemosensory genes. This new information that behavioral response in M. incognita is modulated by specific olfactory genes can be extended to understand chemotaxis in other nematodes.


Subject(s)
Chemotaxis , Tylenchoidea , Animals , Behavior, Animal/physiology , Caenorhabditis elegans/genetics , Chemotaxis/genetics , RNA Interference , Tylenchoidea/genetics , Tylenchoidea/metabolism
10.
J Nepal Health Res Counc ; 16(41): 410-413, 2019 Jan 28.
Article in English | MEDLINE | ID: mdl-30739931

ABSTRACT

BACKGROUND: The Body Mass Index, Waist Circumference and Waist by Hip ratio have linear relation with increase in blood pressure. This study will correlate blood pressure with these anthropometric measures in normal subjects to find out the subtle increase in which of these measure would linearly increase blood pressure. The aim is to find the better anthropometric measure to relate with blood pressure changes. METHODS: One hundred and seventy five healthy medical students were enrolled for the study in Manipal College of Medical Sciences, Pokhara after getting ethical clearance. The mean reading of right brachial arterial blood pressure with mercury manometer in sitting position was taken. For anthropometric measures, body weight was measured in weighing scale and height and circumferences of waist and hip were taken with non elastic measuring tape. The data were used to derive required variables. RESULTS: Out of 175 participants, 59% were male and remaining female. The non obese participants were 46.3% followed by obese (22.9%) as per Asia Pacific Guidelines for The Body Mass Index. The positive correlation of increase in Systolic and Diastolic components of blood pressure was statistically highly significant [P=0.00] in female with normal Waist Circumference and Waist by Hip ratio. However in general, SBP was positively correlated with Waist by Hip ratio [r=0.44] and DBP was positively correlated with Waist Circumference [r=0.43] and were statistically highly significant [P=0.00]. CONCLUSIONS: The Waist Circumference and Waist by Hip Ratio have stronger correlation with blood pressure components than Body Mass Index even in normal subjects.


Subject(s)
Blood Pressure , Body Mass Index , Waist Circumference , Waist-Hip Ratio , Adolescent , Asian People , Cross-Sectional Studies , Female , Humans , Hypertension/pathology , Hypertension/physiopathology , Male , Nepal , Obesity/pathology , Obesity/physiopathology , Sex Factors , Young Adult
11.
JNMA J Nepal Med Assoc ; 56(214): 936-939, 2018.
Article in English | MEDLINE | ID: mdl-31065138

ABSTRACT

INTRODUCTION: The external ear is made up of the elastic cartilage. It is considered constant from the birth till death. Therefore, it's morphological variation plays important role in forensic medicine. The objective of this study was to identify this morphological variation among different nationality and the gender. METHODS: The study was conducted among 50 Nepali students and 50 Indian students of Manipal College of Medical Sciences. The simple random sampling was done. The morphological variation of external ear including different nature of shape of tragus, anti-tragus, lobe and margin of helix were studied on different gender and nationalities. RESULTS: The highest distribution in shape of tragus was round in Nepali 42 (84%) and Indian 37 (74%). Most of Nepali students had flat 26 (52%) shape of anti-tragus and medium for Indian 25 (50%). The maximum ear attached lobe were found in both Nepali and Indian 27 (54%) respectively. Most of the Indian students had elongated shape of helix 24 (48%) whereas in Nepalese round shape of helix 31 (62%). The male participants had maximum round shape of tragus 42 (76.3%), flat shape of anti-tragus 28 (50.9%), free ear lobe 28 (50.9%) and shape of the margin of helix were round 29 (52.7%). The female participants had maximum round shape of tragus 37 (82.2%), medium shape of anti-tragus 22 (48.8%), attached ear lobe 27 (60%), and round shape of margin of helix 25 (55.56%). CONCLUSIONS: The morphology of the external ear varies with each individual. However, it shows it couldn't differentiate their nationalities and gender.


Subject(s)
Anatomic Variation , Ear, External/anatomy & histology , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , India/ethnology , Male , Nepal/ethnology , Schools, Medical , Sex Factors , Students, Medical , Young Adult
12.
Gene ; 619: 50-60, 2017 Jul 01.
Article in English | MEDLINE | ID: mdl-28366833

ABSTRACT

The rice root-knot nematode, Meloidogyne graminicola, seriously impairs the growth and yield of rice which is an important staple food worldwide. The disruption of neuropeptide signalling leading to attenuation in nematode behaviour and thereby perturbed infection, offers an attractive alternative to control nematodes. In this direction, the present study was aimed at mining of putative FMRFamide-like peptides (FLPs) from the transcriptomic dataset of M. graminicola followed by characterization of those FLPs via sequencing of PCR products, qRT-PCR and Southern hybridization analysis. We have characterized nine flp genes (flp-1, flp-3, flp-6, flp-7, flp-11, flp-12, flp-14, flp-16 and flp-18) and a partial neuropeptide receptor gene (flp-18 GPCR) from M. graminicola in the present study. In addition, in situ localization revealed the expression of flp-1 and flp-7 in neurons posterior to the circumpharyngeal nerve ring of M. graminicola. In vitro silencing of nine flp genes and flp-18 GPCR in M. graminicola J2 and their subsequent infection in rice and wheat roots demonstrated the reduced penetration ability of FLP silenced worms which underscores the potential of the FLPergic system as a broad-spectrum target to manage the root-knot nematode problem in rice-wheat cropping system.


Subject(s)
FMRFamide/genetics , Helminth Proteins/genetics , Tylenchoidea/genetics , Animals , FMRFamide/metabolism , Gene Silencing , Helminth Proteins/metabolism , Oryza/parasitology , Tylenchoidea/pathogenicity , Virulence/genetics
13.
Front Plant Sci ; 8: 473, 2017.
Article in English | MEDLINE | ID: mdl-28424727

ABSTRACT

The complex parasitic strategy of Meloidogyne incognita appears to involve simultaneous expression of its pharyngeal gland-specific effector genes in order to colonize the host plants. Research reports related to effector crosstalk in phytonematodes for successful parasitism of the host tissue is yet underexplored. In view of this, we have used in planta effector screening approach to understand the possible interaction of pioneer genes (msp-18 and msp-20, putatively involved in late and early stage of M. incognita parasitism, respectively) with other unrelated effectors such as cell-wall modifying enzymes (CWMEs) in M. incognita. Host-induced gene silencing (HIGS) strategy was used to generate the transgenic eggplants expressing msp-18 and msp-20, independently. Putative transformants were characterized via qRT-PCR and Southern hybridization assay. SiRNAs specific to msp-18 and msp-20 were also detected in the transformants via Northern hybridization assay. Transgenic expression of the RNAi constructs of msp-18 and msp-20 genes resulted in 43.64-69.68% and 41.74-67.30% reduction in M. incognita multiplication encompassing 6 and 10 events, respectively. Additionally, transcriptional oscillation of CWMEs documented in the penetrating and developing nematodes suggested the possible interaction among CWMEs and pioneer genes. The rapid assimilation of plant-derived carbon by invading nematodes was also demonstrated using 14C isotope probing approach. Our data suggests that HIGS of msp-18 and msp-20, improves nematode resistance in eggplant by affecting the steady-state transcription level of CWME genes in invading nematodes, and safeguard the plant against nematode invasion at very early stage because nematodes may become the recipient of bioactive RNA species during the process of penetration into the plant root.

14.
JNMA J Nepal Med Assoc ; 56(208): 426-31, 2017.
Article in English | MEDLINE | ID: mdl-29453474

ABSTRACT

INTRODUCTION: Blood grouping is conventionally done with invasive method by taking blood samples. The objective of this study is to determine blood group with uninvasive procedure by taking fingerprints of the participants and know the associations between their fingerprints and blood groups. METHODS: Seven hundred participants of both genders with no any age limitation from Manipal Teaching Hospital and Manipal College of Medical Sciences were randomly selected. The blood grouping was done by cross reacting blood sample with the antibodies. The fingerprints were taken with the help of stamp pad imprinting the finger ridges over A4 size white papers. The loop, whorl and arch patterns were studied. RESULTS: O+ve blood group 224 (32%) was most prevalent among 700 participants. The loop pattern was highly distributed 3708 (53%) in all blood groups except in A-ve blood group with highest distribution of whorl 20 (40%). The mean comparisons of specific fingerprint in total and also in individual fingers with different ABO and ABO-Rh blood groups showed no any statistical association with P>0.05. However, the loop distribution in individual finger was highest in right middle finger (M) of B-ve blood group 5 (10%). The whorl distribution in individual finger was highest in right index (I), left thumb (T) and left ring (R) fingers of AB+ve blood group 20 (5.5% each). Similarly, the arch distribution was highest in right index fingers of A-ve blood group 3 (6%). CONCLUSIONS: The mean comparison of different fingerprints with ABO and Rh blood groups showed no significant statistical association concluding fingerprints cannot be used for blood grouping.


Subject(s)
ABO Blood-Group System , Dermatoglyphics , Rh-Hr Blood-Group System , Blood Grouping and Crossmatching , Cross-Sectional Studies , Female , Humans , Male , Nepal
15.
Mater Sci Eng C Mater Biol Appl ; 72: 611-619, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28024628

ABSTRACT

Bortezomib (BTZ) is the first proteasome inhibitor approved by the US-FDA is majorly used for the treatment of newly diagnosed and relapsed multiple myeloma including mantle cell lymphoma. BTZ is hydrophobic in nature and is a major cause for its minimal presence as marketed formulations. The present study reports the design, development and characterization of dendrimer based formulation for the improved solubility and effectivity of bortezomib. The study also equally focuses on the mechanistic elucidation of solubilization by two types of dendrimers i.e. fourth generation of poly (amidoamine) dendrimers (G4-PAMAM-NH2) and fifth generation of poly (propylene) imine dendrimers (G5-PPI-NH2). It was observed that aqueous solubility of BTZ was concentration and pH dependent. At 2mM G5-PPI-NH2 concentration, the fold increase in bortezomib solubility was 1152.63 times in water, while approximately 3426.69 folds increase in solubility was observed at pH10.0, respectively (p<0.05). The solubility of the drug was increased to a greater extent with G5-PPI-NH2 dendrimers because it has more hydrophobic interior than G4-PAMAM-NH2 dendrimers. The release of BTZ from G5-PPI-NH2 complex was comparatively slower than G4-PAMAM-NH2. The thermodynamic treatment of data proved that dendrimer drug complexes were stable at all pH with values of ΔG always negative. The experimental findings were also proven by molecular simulation studies and by calculating RMSD and intermolecular hydrogen bonding through Schrodinger software. It was concluded that PPI dendrimers were able to solubilize the drug more effectively than PAMAM dendrimers through electrostatic interactions.


Subject(s)
Antineoplastic Agents/chemistry , Bortezomib/chemistry , Dendrimers/chemistry , Polypropylenes/chemistry , Antineoplastic Agents/metabolism , Bortezomib/metabolism , Drug Carriers/chemistry , Drug Liberation , Hydrogen Bonding , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Molecular Dynamics Simulation , Solubility , Static Electricity , Thermodynamics , Water/chemistry
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