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Article ; Online: Advancements in transdermal drug delivery: A comprehensive review of physical penetration enhancement techniques.

Gaikwad, Sachin S / Zanje, Abhijit L / Somwanshi, Jeevan D

2024 Volume 652, Page(s) 123856

Abstract: Transdermal drug administration has grown in popularity in the pharmaceutical research community due to its potential to improve drug bioavailability, compliance among patients, and therapeutic effectiveness. To overcome the substantial barrier posed by ... ...

Abstract	Transdermal drug administration has grown in popularity in the pharmaceutical research community due to its potential to improve drug bioavailability, compliance among patients, and therapeutic effectiveness. To overcome the substantial barrier posed by the stratum corneum (SC) and promote drug absorption within the skin, various physical penetration augmentation approaches have been devised. This review article delves into popular physical penetration augmentation techniques, which include sonophoresis, iontophoresis, magnetophoresis, thermophoresis, needle-free injection, and microneedles (MNs) Sonophoresis is a technique that uses low-frequency ultrasonic waves to break the skin's barrier characteristics, therefore improving drug transport and distribution. In contrast, iontophoresis uses an applied electric current to push charged molecules of drugs inside the skin, effectively enhancing medication absorption. Magnetophoresis uses magnetic fields to drive drug carriers into the dermis, a technology that has shown promise in aiding targeted medication delivery. Thermophoresis is the regulated heating of the skin in order to improve drug absorption, particularly with thermally sensitive drug carriers. Needle-free injection technologies, such as jet injectors (JIs) and microprojection arrays, offer another option by producing temporary small pore sizes in the skin, facilitating painless and effective drug delivery. MNs are a painless, minimally invasive method, easy to self-administration, as well as high drug bioavailability. This study focuses on the underlying processes, current breakthroughs, and limitations connected with all of these approaches, with an emphasis on their applicability in diverse therapeutic areas. Finally, a thorough knowledge of these physical enhancement approaches and their incorporation into pharmaceutical research has the potential to revolutionize drug delivery, providing more efficient and secure treatment choices for a wide range of health-related diseases.
MeSH term(s)	Humans ; Administration, Cutaneous ; Skin/metabolism ; Pharmaceutical Preparations ; Epidermis ; Drug Delivery Systems/methods ; Drug Carriers/pharmacology
Chemical Substances	Pharmaceutical Preparations ; Drug Carriers
Language	English
Publishing date	2024-01-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2024.123856
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Article: The Performance of HE4 Alone and in Combination with CA125 for the Detection of Ovarian Cancer in an Enriched Primary Care Population.

Barr, Chloe E / Funston, Garth / Jeevan, David / Sundar, Sudha / Mounce, Luke T A / Crosbie, Emma J

Cancers

2022 Volume 14, Issue 9

Abstract: Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection ...

Abstract	Human epididymis 4 (HE4) is a promising ovarian cancer biomarker, but it has not been evaluated in primary care. In this prospective observational study, we investigated the diagnostic accuracy of HE4 alone and in combination with CA125 for the detection of ovarian cancer in symptomatic women attending primary care. General practitioner (GP)-requested CA125 samples were tested for HE4 at a large teaching hospital in Manchester, and cancer outcomes were tracked for 12 months. We found a low incidence of ovarian cancer in primary care; thus, the cohort was enriched with pre-surgical samples from 81 ovarian cancer patients. The Risk of Ovarian Malignancy Algorithm (ROMA) was calculated using age (</>51) as a surrogate for menopause. Conventional diagnostic accuracy metrics were determined. A total of 1229 patients were included; 82 had ovarian cancer. Overall, ROMA performed best (AUC-0.96 (95%CI: 0.94−0.98, p = <0.001)). In women under 50 years, the combination of CA125 and HE4 (either marker positive) was superior (sensitivity: 100% (95%CI: 81.5−100.0), specificity: 80.1% (95%CI 76.7−83.1)). In women over 50, ROMA performed best (sensitivity: 84.4% (95%CI: 73.1−92.2), specificity: 87.2% (95%CI 84.1−90)). HE4 and ROMA may improve ovarian cancer detection in primary care, particularly for women under 50 years, in whom diagnosis is challenging. Validation in a larger primary care cohort is required.
Language	English
Publishing date	2022-04-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14092124
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Article ; Online: Then and now: outcomes of surgical treatment for early cervical cancer 1902.

Jeevan, David / Oláh, Karl

BJOG : an international journal of obstetrics and gynaecology

2015 Volume 122, Issue 11, Page(s) 1524

MeSH term(s)	Cervix Uteri/surgery ; Early Diagnosis ; Female ; Gynecologic Surgical Procedures/trends ; Gynecology/trends ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; Hysterectomy/trends ; Laparoscopy ; Lymph Node Excision ; Robotic Surgical Procedures ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/mortality ; Uterine Cervical Neoplasms/surgery
Language	English
Publishing date	2015-10
Publishing country	England
Document type	Historical Article ; Journal Article
ZDB-ID	2000931-8
ISSN	1471-0528 ; 0306-5456 ; 1470-0328
ISSN (online)	1471-0528
ISSN	0306-5456 ; 1470-0328
DOI	10.1111/1471-0528.13473
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Article ; Online: Minimizing Radiation Exposure in Evaluation of Pediatric Head Trauma: Use of Rapid MR Imaging.

Mehta, H / Acharya, J / Mohan, A L / Tobias, M E / LeCompte, L / Jeevan, D

AJNR. American journal of neuroradiology

2015 Volume 37, Issue 1, Page(s) 11–18

Abstract: Background and purpose: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to ... ...

Abstract	Background and purpose: With >473,000 annual emergency department visits for children with traumatic brain injuries in the United States, the risk of ionizing radiation exposure during CT examinations is a real concern. The purpose of this study was to assess the validity of rapid MR imaging to replace CT in the follow-up imaging of patients with head trauma. Materials and methods: A retrospective review of 103 pediatric patients who underwent initial head CT and subsequent follow-up rapid MR imaging between January 2010 and July 2013 was performed. Patients had minor head injuries (Glasgow Coma Scale, >13) that required imaging. Initial head CT was performed, with follow-up rapid MR imaging completed within 48 hours. A board-certified neuroradiologist, blinded to patient information and scan parameters, then independently interpreted the randomized cases. Results: There was almost perfect agreement in the ability to detect extra-axial hemorrhage on rapid MR imaging and CT (κ = 0.84, P < .001). Evaluation of hemorrhagic contusion/intraparenchymal hemorrhage demonstrated a moderate level of agreement between MR imaging and CT (κ = 0.61, P < .001). The ability of MR imaging to detect a skull fracture also showed a substantial level of agreement with CT (κ = 0.71, P < .001). Detection of diffuse axonal injury demonstrated a slight level of agreement between MR imaging and CT (κ = 0.154, P = .04). However, the overall predictive agreement for the detection of an axonal injury was 91%. Conclusions: Rapid MR imaging is a valid technique for detecting traumatic cranial injuries and an adequate examination for follow-up imaging in lieu of repeat CT.
MeSH term(s)	Adolescent ; Brain Injuries/diagnosis ; Child ; Child, Preschool ; Emergency Service, Hospital ; Female ; Humans ; Infant ; Magnetic Resonance Imaging/methods ; Male ; Pediatrics/methods ; Radiation Exposure/prevention & control ; Retrospective Studies ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2015-09-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	603808-6
ISSN	1936-959X ; 0195-6108
ISSN (online)	1936-959X
ISSN	0195-6108
DOI	10.3174/ajnr.A4464
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Article ; Online: Postpartum ovarian vein thrombosis in a 29-year-old woman with ulcerative colitis.

Bhandari, Harish M / Jeevan, David / Slinn, Jessica / Goswami, Kavita

BMJ case reports

2014 Volume 2014

Abstract: A 29-year-old woman with known ulcerative colitis developed a right-sided abdominal pain a day after preterm vaginal delivery at 30 weeks. She did not have any nausea, vomiting and had normal bowel movements. The observations were within normal limits ... ...

Abstract	A 29-year-old woman with known ulcerative colitis developed a right-sided abdominal pain a day after preterm vaginal delivery at 30 weeks. She did not have any nausea, vomiting and had normal bowel movements. The observations were within normal limits and white cell counts were marginally elevated with a normal C reactive protein. A large ovarian vein thrombosis on the left side was an incidental finding on a CT of the abdomen and pelvis undertaken to establish the cause for abdominal pain. The patient was managed by a multidisciplinary team and was treated with anticoagulants for 6 months. This case illustrates that the incidence of pelvic venous thrombosis may be higher in pregnancy and puerperium.
MeSH term(s)	Abdominal Pain/etiology ; Adult ; Colitis, Ulcerative/complications ; Colitis, Ulcerative/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Ovary/blood supply ; Pregnancy ; Puerperal Disorders/diagnostic imaging ; Puerperal Disorders/etiology ; Thrombosis/diagnostic imaging ; Thrombosis/etiology ; Tomography, X-Ray Computed
Language	English
Publishing date	2014-12-03
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2014-206452
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Article: Detailed analysis of the region 9-30 of rat follicle stimulating hormone receptor: identification of peptide 20-30 as a potential hormone binding inhibitor.

Ghosalkar, Jeevan D / Mahale, Smita D

Peptides

2006 Volume 27, Issue 11, Page(s) 2894–2900

Abstract: The extracellular domain (ECD) of the follicle stimulating hormone receptor (FSHR) has been shown to be a major determinant of hormone selectivity. The N-terminal 9-30 region, the sequence of which is unique to FSHR, has been extensively studied earlier ... ...

Abstract	The extracellular domain (ECD) of the follicle stimulating hormone receptor (FSHR) has been shown to be a major determinant of hormone selectivity. The N-terminal 9-30 region, the sequence of which is unique to FSHR, has been extensively studied earlier and has been proposed to be an FSHR neutralizing epitope. In this study antipeptide antibodies specific to the peptide 9-30 were generated and used for identifying a specific immunodominant region within it. Overlapping peptides corresponding to the regions 9-19, 15-25 and 20-30 were synthesized. The ability of the antipeptide antibodies to 9-30 of FSHR to bind to different peptides was checked. The results indicated that the antibodies mainly recognized the peptide 20-30 and not the other two overlapping peptides. Further, the effect of the peptide 20-30 on the binding of radiolabeled FSH to its receptor was monitored. This peptide showed FSH-binding inhibitory activity with an IC(50) value of 0.598 x 10(-4)M and was more effective than the peptide 9-30 itself. Binding kinetics revealed that the observed effect of the peptide 20-30 is due to mixed type of inhibitory mechanism. This is the smallest peptide from the rat FSHR sequence having ability to inhibit FSH binding to its receptor by more than 90%.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies/pharmacology ; Antibody Specificity ; Binding Sites/physiology ; Binding, Competitive/drug effects ; Binding, Competitive/immunology ; Blotting, Western ; Epitope Mapping ; Humans ; Immunodominant Epitopes ; Molecular Sequence Data ; Peptide Fragments/chemistry ; Peptide Fragments/genetics ; Peptide Fragments/immunology ; Peptide Fragments/isolation & purification ; Peptide Fragments/metabolism ; Protein Binding ; Rabbits ; Rats ; Receptors, FSH/chemistry ; Receptors, FSH/genetics ; Receptors, FSH/immunology ; Receptors, FSH/metabolism
Chemical Substances	Antibodies ; Immunodominant Epitopes ; Peptide Fragments ; Receptors, FSH ; follicle stimulating hormone receptor (20-30), rat ; follicle stimulating hormone receptor (9-30), rat
Language	English
Publishing date	2006-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2006.05.027
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Article ; Online: Involvement of mTOR signaling pathways in regulating growth and dissemination of metastatic brain tumors via EMT.

Kwasnicki, Amanda / Jeevan, Dhruve / Braun, Alex / Murali, Raj / Jhanwar-Uniyal, Meena

Anticancer research

2015 Volume 35, Issue 2, Page(s) 689–696

Abstract: Background: Metastatic dissemination to the brain may involve a process termed epithelial-mesenchymal transition (EMT), which results in a migratory, invasive and proliferative cell phenotype. Recent studies suggest that Mechanistic target of rapamycin ( ...

Abstract	Background: Metastatic dissemination to the brain may involve a process termed epithelial-mesenchymal transition (EMT), which results in a migratory, invasive and proliferative cell phenotype. Recent studies suggest that Mechanistic target of rapamycin (mTOR, that exists in two multi-protein complexes (mTORC1 and mTORC2), may regulate EMT, in addition to controlling cell growth, survival, metabolism and motility. However, the role of mTOR in brain metastases remains elusive. We hypothesize that mTOR plays a crucial role in the process of EMT in brain metastasis and therefore serves as a target of therapy. Materials and methods: Immunohistochemical analyses were performed to determine the expression of components of mTOR pathways. Immunofluorescence and immunoblotting were executed to determine the markers of EMT after treatments with siRNA or inhibitors of mTOR pathways. Cell proliferation using MTT, S-phase entry by determining EdU-incorporation, chemotactic and scratch-wound migration assays were performed. Results: Metastatic tumor samples expressed components of mTOR pathways, namely, mTOR, Raptor and Rictor with a significant overlap. Metastatic potential was enhanced in an astrocytic environment and suppressed following mTOR inhibition. mTOR inhibition resulted in nuclear localization of the epithelial marker of EMT, E-cadherin, and enhancement in expression of the mesenchymal marker vimentin. Conclusion: Results suggest that the mTOR pathway is activated in metastatic brain tumors, and inhibition of mTOR signaling could provide therapeutic value in the management of patients with brain metastases.
MeSH term(s)	Base Sequence ; Biomarkers, Tumor/metabolism ; Blotting, Western ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Division ; DNA Primers ; Epithelial-Mesenchymal Transition ; Fluorescent Antibody Technique ; Humans ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Multiprotein Complexes/metabolism ; Neoplasm Metastasis ; RNA, Small Interfering ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism
Chemical Substances	Biomarkers, Tumor ; DNA Primers ; Multiprotein Complexes ; RNA, Small Interfering ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1)
Language	English
Publishing date	2015-02
Publishing country	Greece
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: Characterization of peptide 20-30 of follicle stimulating hormone receptor as an antagonist of receptor activity: significance of charged residues.

Dupakuntla, Madhavi / Ghosalkar, Jeevan D / Mahale, Smita D

Chemical biology & drug design

2009 Volume 73, Issue 1, Page(s) 108–114

Abstract: We had previously reported the region (20-30) from follicle stimulating hormone receptor as being an immunodominant epitope and the smallest reported peptide capable of inhibiting hormone binding. We now report it to be an effective antagonist of ligand- ... ...

Abstract	We had previously reported the region (20-30) from follicle stimulating hormone receptor as being an immunodominant epitope and the smallest reported peptide capable of inhibiting hormone binding. We now report it to be an effective antagonist of ligand-induced cAMP signalling as well. The region (20-30) of follicle stimulating hormone receptor has three charged residues, namely, E(22), D(26) and R(29) that are specific to follicle stimulating hormone receptor and are conserved in mammals. This study aimed to verify whether the charged residues contribute to the activity of the follicle stimulating hormone receptor peptide (20-30). This was done using analogs of follicle stimulating hormone receptor peptide (20-30), each having an alanine substitution for a corresponding charged residue. The analog peptides displayed a loss of activity and could not inhibit hormone binding or the subsequent signal transduction. The ability of follicle stimulating hormone receptor peptide (20-30) to bind antipeptide antibodies against follicle stimulating hormone receptor peptide (9-30) was either decreased or abolished with the alanine substituted analog peptides of follicle stimulating hormone receptor peptide (20-30). The loss of function led us to verify whether there was a conformational change as well. CD spectral analysis did not reveal a significant change. These observations indicate that the charged aminoacids present in follicle stimulating hormone receptor peptide (20-30) are crucial for the observed follicle stimulating hormone antagonistic activity. This information could form the basis for the design of novel compounds capable of functioning as follicle stimulating hormone antagonists.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies/metabolism ; Cyclic AMP/metabolism ; Female ; Follicle Stimulating Hormone/antagonists & inhibitors ; Follicle Stimulating Hormone/metabolism ; Male ; Models, Molecular ; Molecular Sequence Data ; Peptides/chemistry ; Peptides/genetics ; Peptides/metabolism ; Protein Structure, Tertiary ; Rats ; Receptors, FSH/chemistry ; Receptors, FSH/genetics ; Receptors, FSH/metabolism
Chemical Substances	Antibodies ; Peptides ; Receptors, FSH ; Follicle Stimulating Hormone (9002-68-0) ; Cyclic AMP (E0399OZS9N)
Language	English
Publishing date	2009-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2216600-2
ISSN	1747-0285 ; 1747-0277
ISSN (online)	1747-0285
ISSN	1747-0277
DOI	10.1111/j.1747-0285.2008.00748.x
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Article: Characterization of Peptide 20-30 of Follicle Stimulating Hormone Receptor as an Antagonist of Receptor Activity: Significance of Charged Residues

Dupakuntla, Madhavi / Ghosalkar, Jeevan D / Mahale, Smita D

Chemical biology & drug design. 2009 Jan., v. 73, no. 1

2009

Abstract	We had previously reported the region (20-30) from follicle stimulating hormone receptor as being an immunodominant epitope and the smallest reported peptide capable of inhibiting hormone binding. We now report it to be an effective antagonist of ligand-induced cAMP signalling as well. The region (20-30) of follicle stimulating hormone receptor has three charged residues, namely, E²², D²⁶ and R²⁹ that are specific to follicle stimulating hormone receptor and are conserved in mammals. This study aimed to verify whether the charged residues contribute to the activity of the follicle stimulating hormone receptor peptide (20-30). This was done using analogs of follicle stimulating hormone receptor peptide (20-30), each having an alanine substitution for a corresponding charged residue. The analog peptides displayed a loss of activity and could not inhibit hormone binding or the subsequent signal transduction. The ability of follicle stimulating hormone receptor peptide (20-30) to bind antipeptide antibodies against follicle stimulating hormone receptor peptide (9-30) was either decreased or abolished with the alanine substituted analog peptides of follicle stimulating hormone receptor peptide (20-30). The loss of function led us to verify whether there was a conformational change as well. CD spectral analysis did not reveal a significant change. These observations indicate that the charged aminoacids present in follicle stimulating hormone receptor peptide (20-30) are crucial for the observed follicle stimulating hormone antagonistic activity. This information could form the basis for the design of novel compounds capable of functioning as follicle stimulating hormone antagonists.
Keywords	peptides
Language	English
Dates of publication	2009-01
Size	p. 108-114.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	2216600-2
ISSN	1747-0285 ; 1747-0277
ISSN (online)	1747-0285
ISSN	1747-0277
DOI	10.1111/j.1747-0285.2008.00748.x
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Article ; Online: Deconstructing mTOR complexes in regulation of Glioblastoma Multiforme and its stem cells.

Jhanwar-Uniyal, Meena / Jeevan, Dhruve / Neil, Jayson / Shannon, Craig / Albert, Ladislau / Murali, Raj

Advances in biological regulation

2013 Volume 53, Issue 2, Page(s) 202–210

Abstract: Atypical serine-threonine kinase, mTOR (mechanistic target of Rapamycin; originally coined "mammalian TOR"), exists in two distinct multi-protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), that senses and integrates a variety of ... ...

Abstract	Atypical serine-threonine kinase, mTOR (mechanistic target of Rapamycin; originally coined "mammalian TOR"), exists in two distinct multi-protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), that senses and integrates a variety of environmental signals to control organism growth and homeostasis via non-overlapping signaling pathways. mTOR belongs to the phosphoinositide 3-kinase (PI3-K)-related kinase family, and an aberrant activation of mTORC1 is a potential contributing factor in uncontrolled cell growth, proliferation, and survival of tumor cells via specific effects on cap-dependent translation initiation, as well as in a more sustained manner via advancing ribosome biogenesis. It is thereby shown to be deregulated in numerous pathological conditions including cancer, obesity, type 2 diabetes, and neurodegeneration. Notably, mTOR itself, or through its substrates, regulates stem cell differentiation and maintenance of plueropotency. mTORC2 has been linked to cytoskeletal reorganization and cell survival through Akt, and is crucial to many divergent physiological functions, which may include stem cell regulation.
MeSH term(s)	Cell Differentiation ; Glioblastoma/drug therapy ; Glioblastoma/physiopathology ; Humans ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Multiprotein Complexes/physiology ; Neoplasms/physiopathology ; Proto-Oncogene Proteins c-akt/physiology ; Sirolimus/therapeutic use ; Stem Cells/drug effects ; Stem Cells/physiology ; TOR Serine-Threonine Kinases/physiology
Chemical Substances	Multiprotein Complexes ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2013-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2012.10.001
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