International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
International Journal of Pharmaceutical Science Invention (IJPSI)inventionjournals
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online
Uterine Fibroids: Symptoms, Causes, Risk Factors & Treatment uterine fibroids aren't associated with an increased risk of uterine cancer and almost never develop into cancer
ENDOMETRIOSIS UPDATEFocus on Dienogest Dr Sharda jain dr Jyoti Agarwal Lifecare Centre
ENDOMETRIOSIS UPDATEFocus on Dienogest
AGENDA
Background
What’s New in Endometriosis
Clinical Discussions in Managing Endometriosis
Newer Evidences on Dienogest
Hysterectomy vs levonorgestrel inter-uterine device
Hysterectomy was the most cost-effective treatment
Progesterone receptor modulators for the treatment of uterine fibroids
Progesterone receptor modulators (ulipristal acetate or mifepristone) were also identified as a potential new treatment by members of the Guideline Development group (GDG)
Pre-surgical medical treatment of uterine fibroids (progesterone receptor modulaters and gonadotrophin releasing hormone analogues)
The new evidence may favour ulipristal acetate over gonadotrophin releasing hormone analogue for some, but not all outcomes as a pre-treatment for uterine fibroids before myomectomy
Uterine Fibroids: Symptoms, Causes, Risk Factors & Treatment uterine fibroids aren't associated with an increased risk of uterine cancer and almost never develop into cancer
ENDOMETRIOSIS UPDATEFocus on Dienogest Dr Sharda jain dr Jyoti Agarwal Lifecare Centre
ENDOMETRIOSIS UPDATEFocus on Dienogest
AGENDA
Background
What’s New in Endometriosis
Clinical Discussions in Managing Endometriosis
Newer Evidences on Dienogest
Hysterectomy vs levonorgestrel inter-uterine device
Hysterectomy was the most cost-effective treatment
Progesterone receptor modulators for the treatment of uterine fibroids
Progesterone receptor modulators (ulipristal acetate or mifepristone) were also identified as a potential new treatment by members of the Guideline Development group (GDG)
Pre-surgical medical treatment of uterine fibroids (progesterone receptor modulaters and gonadotrophin releasing hormone analogues)
The new evidence may favour ulipristal acetate over gonadotrophin releasing hormone analogue for some, but not all outcomes as a pre-treatment for uterine fibroids before myomectomy
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
What is greenhouse gasses and how many gasses are there to affect the Earth.moosaasad1975
What are greenhouse gasses how they affect the earth and its environment what is the future of the environment and earth how the weather and the climate effects.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Comparing Evolved Extractive Text Summary Scores of Bidirectional Encoder Rep...University of Maribor
Slides from:
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Track: Artificial Intelligence
https://www.etran.rs/2024/en/home-english/
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
https://www.youtube.com/channel/UCAiarMZDNhe1A3Rnpr_WkzA/videos
Thanks...!
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
2. Definition:
Presence of endometrial-type mucosa outside uterine cavity
Predominantly, but not exclusively, in pelvic compartment
Estrogen-dependent chronic inflammatory condition that
affects women in their reproductive period
Associated with pelvic pain & infertility
Vercellini P, et al. Nat. Rev. Endocrinol. 10, 261–275 (2014)
3. Determination of prevalence & incidence figures has been
hampered by exclusive reliance upon surgical visualization of
lesions for definite diagnosis
Real incidence of endometriosis is unknown
Estimated: Present in more than 15% of reproductive age
women & in up to 50% of women with pelvic pain
Vercellini P, et al. Nat. Rev. Endocrinol. 10, 261–275 (2014)/ Maestre EN, et al. Fertil Steril. 2012; 98: 1209-17.
6. Angiogenesis, arteriogenesis or vessel maturation &
lymphangiogenesis comprise continuum of vascular
development with overlap and interaction between
mechanisms by which they are controlled
Rogers PAW, et al. Reproductive Sciences Vol. 16 No. 2 February 2009 147-151.
These processes are of clinical interest because they play roles in
endometrial repair, placental development and in gynecological
disorders including endometrial cancer, endometriosis &
abnormal uterine bleeding
8. • Peritoneal fluid of patients with endometriosis is complex suspension
carrying inflammatory cytokines, growth factors, steroid hormones,
proangiogenic factors, macrophages, and endometrial and red blood cells
• These cells & their signaling products concur to promote spreading of new
blood vessels at endometriotic lesions and surroundings which contributes
to endometriotic implant survival
• Experimental studies of several antiangiogenic agents demonstrated
regression of endometriotic lesions by reducing their blood supply
9. Standard medical therapies for patients with endometriosis:
Analgesics (NSAIDs or acetaminophen
OCPs
Androgenic agents (e.g., danazol, progestogens (e.g.,
medroxyprogesterone acetate)
Gonadotropin-releasing hormone analogues (GnRHas; e.g.,
leuprolide, goserelin, triptorelin, nafarelin) &
Antiprogestogens (e.g., gestrinone)
Mounsey AL, et al. Am Fam Physician. 2006; 74: 594-600.
10. NSAIDs Nausea, vomiting, gastrointestinal irritation,
drowsiness, headache
Combined oral contraceptives Nausea, weight gain, fluid retention, depression,
breakthrough bleeding, breast tenderness,
headache, decreased menstrual flow
Progestins Nausea, weight gain, fluid retention, breakthrough
bleeding, depression, amenorrhea, delayed return of
ovulation
GnRH agonists Hypoestrogenism (vasomotor symptoms, vaginal
dryness, decreased libido, irritability, loss of bone
mineral density)
Aromatase inhibitors Hypoestrogenism, induction of ovulation
Danazol Hyperandrogenic side effects (acne, edema,
decreased breast size)
Giudice LC. N Engl J Med 2010;362:2389-98.
11. Fulguration, ablation, &
excision
Risk associated with anesthesia and risk of infection,
damage to internal organs, new adhesions,
hemorrhage
Excision or drainage &
ablation
Risk associated with anesthesia and risk of infection,
damage to internal organs, new adhesions,
hemorrhage
LPSN, nerve-pathway
interruption (with
conservative surgery)
Bleeding in the adjacent venous plexus, urinary
urgency, constipation, painless first-stage labor
Hysterectomy, bilateral
oophorectomy (abdominal,
laparoscopic, total, or
supracervical)
Persistent or recurrent pain in 10% of patients,
residual ovarian tissue
Giudice LC. N Engl J Med 2010;362:2389-98.
12.
13. Emerging evidence that estrogens can both promote & inhibit
endometrial vessel growth under different circumstances,
demonstrates the complex regulation of endometrial
angiogenesis
During angiogenic process endothelial cells proliferate,
migrate & attach to external cellular matrix, inducing matrix
remodeling and formation of new lumen in endometrium of
women with endometriosis
Luisi S, et al. Archives of Perinatal Medicine 20(2), 69-72, 2014.
14. Different antiangiogenetic treatments such as anti-VEGF
agents & other angiostatic drugs have been tested in
experimental models of endometriosis with successful results
inhibiting new vessels formation
These drugs, mainly with cytotoxic properties, target
specifically endothelial cells without penetrate in tissues
Luisi S, et al. Archives of Perinatal Medicine 20(2), 69-72, 2014.
15. Dopamine & dopamine agonists (bromocriptine, cabergoline) are
able to promote VEGFR-2 endocitosis in endothelial cells, blocking
critical step in neoangiogenesis process & reducing expression of
VEGF in ectopic endometrium
Thiazolidinediones: Class of medications used in treatment of Type
2 DM & have been shown to inhibit both monocyte migration and
peritoneal inflammatory cells in mouse model and modulate
angiogenesis
Small trial (limited series of patients) endometriosis treated with
rosiglitazone for 6 months: Possibility of using TZDs for
endometriosis pain relief in conjunction with attempts to conceive
Luisi S, et al. Archives of Perinatal Medicine 20(2), 69-72, 2014.
16. Rocha ALL, et al. Obstetrics and Gynecology International. Volume 2013, Article ID 859619, 8 pages.
17. Rocha ALL, et al. Obstetrics and Gynecology International. Volume 2013, Article ID 859619, 8 pages.
18. Idea to use dopamine agonists as anti-angiogenic
agents began with study by Basu S. et al
1st reported that neurotransmitter dopamine strongly &
selectively inhibits vascular permeabilizing and angiogenic
activities of vascular permeability factor (VPF)/VEGA at non-
toxic levels
Ercan MC, et al. Arch Gynecol Obstet (2015) 291:1103–1111.
19. Hamid AM et al. Arch Gynecol Obstet. 2014 Oct; 290(4): 677-82..
20. RCT on 140 patients
Group 1: Cabergoline 0.5
mg twice a week for 12
weeks (n=71)
Group 2: LHRH, 3
injections, once per
month (n=69)
Hamid AM et al. Arch Gynecol Obstet. 2014 Oct; 290(4): 677-82..
21. Cabergoline is more effective than LHRH agonist in decreasing
endometrioma size >25% of its original size
Hamid AM et al. Arch Gynecol Obstet. 2014 Oct; 290(4): 677-82..
Side effects in both groups:
Not severe & did not require stoppage of study in any patient
Dosage: 0.5 mg
twice a week
for 12 weeks
22. Hamid AM et al. Arch Gynecol Obstet. 2014 Oct; 290(4): 677-82..
Basis of success of Cabergoline in controlling
endometrioma:
Apparently due to diminishing VEGF, thus dealing with
main pathophysiology of endometriosis spread
24. Usmani F et al. International Journa;l of Multidisciplinary Research and Development. 2015; 2(5): 406-408.
1. In endometriosis patients who desired fertility, Cabergoline
therapy offers clear cut advantage over others forms of
therapy available, which delays conception by their
mechanism of actions
2. Cabergoline can be used preoperatively, postoperatively,
alone or in combination with COCs
25. 3. No adjuvant therapy is needed as it does not bring
hypoestrogenic & bone density changes
4. Effective in endometriotic patients with elevated prolactin
levels
5. Reduces pain by its action on nerve fibre
Usmani F et al. International Journa;l of Multidisciplinary Research and Development. 2015; 2(5): 406-408.
26. Usmani F et al. International Journa;l of Multidisciplinary Research and Development. 2015; 2(5): 406-408.
Clear advantage:
Other forms of therapies delay conception by their
mechanism of actions & usually don`t give pain relief
While cabergoline through its action on nerve
fibers decreases pain as well
27. Aim – Evaluate anti-angiogenic properties of Cabergoline on the
growth of established endometriosis lesions and to investigate the
molecular mechanisms by which Cabergoline exerts its anti-
angiogenic effect.
Methods: Human endometrium fragments were implanted in female
nude mice peritoneum, and mice were treated with vehicle, 0.05 or
0.1 mg/kg/day oral Cb2 for 14 days.
Parameters: After treatment, the implants were processed to assess
proliferative activity, neoangiogenesis, VEGFR-2 phosphorylation and
angiogenic gene expression.
28. a) Cabergoline ensures significant regression of active
lesions and cell proliferation
Recovered active lesions was
significantly (P , 0.05) decreased
when low- (58.6+9.7%) or high-
(60.4+8.4%) dose Cabergoline
was employed as compared with
the controls. Proliferation index measures
proliferative activity of
endometriotic cells
29. Ang-1 and Wnt-1 expression (antiangiogenic factors) were
significantly increased by Cabergoline low and high dose
as compared to controls.
31. “These findings support the testing of
dopamine agonists as a novel therapeutic
approach to peritoneal endometriosis in
humans”
32.
33. Conclusion of the review article:
Biomedicine & Pharmacotherapy (March 2017)
Ref: Biomedicine & Pharmacotherapy 90 (2017) 575–585
34. Salient points discussed in the article:
Current therapy has limitations like
• Risk of recurrence
• Side effects
Cabergoline as an effective option for endometriosis treatment
• Cabergoline reduces endometriosis size by its anti angiogenic action
• Reduces expression the VEGF and VEFG receptor proteins.
• Undesired Contraceptive action
• Cost of therapy
Fertility Sterility March 2017
Ref: Fertil Steril2017;107:555–65
35. Clinical trial for publication and reprint:
1. Cabergoline v/s medroxiprogeserone in endometriosis
Study conducted by Dr Amit Koel, Kolkata medical college,
Kolkata
Cabergoline is compared with Medroxy progesterone for
treatment of pain associated with endometriosis
35
39. Study highlights the role of Cabergoline to target
neoangiogenesis in Endometriosis
40. Limitations of currently available hormonal therapies & surgeries
• The currently prescribed hormonal therapies are associated with significant
side-effects & evidence supporting their efficacy is still limited.
• High rate of recurrence is seen after surgery, and appropriate second
preventive therapy is currently recommended.
• Many women gain only partial or intermittent improvement in the
symptoms.
41. Cabergoline effect on Endometrial implants
• Cabergoline a safe & effective dopamine agonist causes endocytosis of VEGFR-
2, thus halting the VEGF & VEGFR-2 binding leading to reduction in
Neoangeogenesis.
• Exposure to Cabergoline was associated with Decreased number of active
lesions, lowered cellularity, and a significantly less developed vascularization.
• Stimulation by cabergoline was associated to reduce phosphorylation of
VEGFR2, to reduced gene and protein expression of vascular endothelial
growth factor, and increased level of antiangiogenic markers.
42. Cabergoline: Yields better results in decreasing size of
endometrioma compared to LHRH by exerting
antiangiogenic effects through VEGFR-2 inactivation
No major side effects
Easy to administer
Cheaper than LHRH-agonist
Reduces pelvic pain associated with endometriosis
significantly
Can be tried as 1st line medical therapy in
endometriomas before resorting to laparoscopic
excision
Hamid AM et al. Arch Gynecol Obstet. 2014 Oct; 290(4): 677-82..
Conclusion