This document discusses the pathophysiology and treatment of bacterial meningitis. It begins by defining bacterial meningitis as an inflammation of the meninges caused by bacterial invasion. It then discusses the pathogenesis, which involves bacterial invasion across the blood-brain barrier, an inflammatory response, and neuronal damage caused by bacterial toxins and immune responses. Clinical diagnosis is based on nonspecific symptoms but is confirmed by cerebrospinal fluid analysis showing inflammation. Treatment involves immediate empirical antibiotics along with corticosteroids to reduce inflammation and intracranial pressure.
Definition of neonatal sepsis,type of neonatal sepsis ,early onset neonatal sepsis,late onset neonatal sepsis,Pathophysiology of neonatal sepsis,,sign and symptoms of neonatal sepsis, diagnosis of neonatal sepsis,management of neonatal sepsis, antibiotic used for neonatal sepsis,prevention of neonatal sepsis, prognosis of neonatal sepsis ,and A summary
Definition of neonatal sepsis,type of neonatal sepsis ,early onset neonatal sepsis,late onset neonatal sepsis,Pathophysiology of neonatal sepsis,,sign and symptoms of neonatal sepsis, diagnosis of neonatal sepsis,management of neonatal sepsis, antibiotic used for neonatal sepsis,prevention of neonatal sepsis, prognosis of neonatal sepsis ,and A summary
Pediatric Triage
French verb “trier”, means to separate or select.
Triage is the process of rapid assessment of a patient with a view to define urgency of care & priorities in treatment.
It helps in rational allocation of limited resources, when demand exceeds availability.
Triage is the first step in the management of a sick child admitted to a hospital.
Acute meningoencephalitis Powerpoint presentation.
It comprises of acute meningitis and acute encephalitis, their clinical features, physical assesment, diagnosis and treatment.
Pediatric Triage
French verb “trier”, means to separate or select.
Triage is the process of rapid assessment of a patient with a view to define urgency of care & priorities in treatment.
It helps in rational allocation of limited resources, when demand exceeds availability.
Triage is the first step in the management of a sick child admitted to a hospital.
Acute meningoencephalitis Powerpoint presentation.
It comprises of acute meningitis and acute encephalitis, their clinical features, physical assesment, diagnosis and treatment.
A case presentation of Tuberculous Meningitis. Management Included. This patient had experienced Drug-induced Hepatitis because of prescription reading error
central nervous infection for clinical pharmacists and other medical students this contains management of cns infections how it can be diagnosed and how to chose appropriate drug treatment based on age of patient.
There are nearly 100 viruses of the herpes group that infect many different animal species.
Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV)
herpes simplex virus types 1 (HHV 1)
Herpes simplex virus type 2 (HHV 2)
Varicella-zoster virus (HHV 3)
Epstein-Barr virus, (HHV 4)
Cytomegalovirus (HHV 5)
Human herpesvirus 6 (HHV 6)
Human herpesvirus 7 (HHV 7)
Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus).
Herpes B virus of monkeys can also infect humans
hELMINTHS#corona virus#Aspergillosis#BUGANDO#CUHAS#CUHAS#CUHAS#CNS INFECTIONS
Identify the most common parasitic diseases that affect the CNS.
Discuss the Imaging features of these diseases.
Clarify the significances of Imaging in diagnosis and assessment of pathological features of these diseases.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
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 .
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Pathophysiology and Treatment of Meningoencephalitis - A journal reading
1. Pathophysiology and Treatment
of Bacterial Meningitis
Hoffman Olaf and Weber Joerg R.
Department of Neurology, Charite-Universitaetsmedizin Berlin, Germany, Department of Cell Biology
and Neurobiology, Charite—Universitaetsmedizin Berlin Germany, Department of Neurology, LKH,
Klagenfurt, Austria
Presented by:
Renol
Septa Tio Emeralda S
Facilitator :
Dr. Sudin Sitanggang, Sp.S
Kepaniteraan Klinik Neurologi
Fakultas Kedokteran
Universitas Kristen Indonesia
RS Cikini
2. INTRODUCTION
• Antibiotics and Critical care in Bacterial
Meningitis is still an unresolved problem
• Highly Effective antibiotics kill bacteria
efficiently, but mortality rates are still up to
34% (van de Beek et al. 2006)
• Up to 50% of the survivors suffer from long
term sequelae (weisfelt et al.2006)
3. INTRODUCTION
• Decreasing inflammation in acute bacterial
meningitis using dexamethasone doesn’t
show any positive result in poor countries
underlying disease tb, AIDS, malnutrition?
4. DEFINITION OF BACTERIAL MENINGITIS
• Bacterial meningitis is an inflammation of the meninges, in
particular the arachnoid and the pia mater, associated with
the invasion of bacteria into the subarachnoid space,
principles known for more than 100 years [Flexner, 1907]
• A hallmark of bacterial meningitis is the recruitment of highly
activated leukocytes into the CSF
• In the recent years the damage of the neurons, particularly in
hippocampal structures, has been identified as a potential
cause of persistent neuropsychological deficits in survivors
[Zysk et al. 1996; Nau et al. 1999b]
5. EPIDEMIOLOGY
• Formerly BM cause Haemophillus Influenzae
• Present BM cause Neisseria meningitides (common)
• In addition to classical meningitis, meningococci
frequently cause systemic disease including fulminant
gram-negative sepsis and DIC
• Predisposing factors = former splenectomy,
malnutrition or sickle disease
• WHO estimates at least 500.000 newly symptomatic
infections per year worldwide, leading to at least
50.000 deaths (Stephens et al. 2007)
• The highest incidence Sub-Sahara meningitis belt
where cyclic epidemics at least once per decade
6. PATHOGENESIS
• Bacterial Invasion (1);
– Bacteria direct accesses (dural defects; local
infection) invades from the blood stream to
CNS
– Anatomical site unidentified
• Several highly vascularized sites are potential entry
locations
• In order to cross the blood brain or the blood; CSF
barrier and to overcome sophisticated structures such
as tight junctions, meningeal pathogens must carry
effective molecular tools.
7. PATHOGENESIS
• Bacterial Invasion(2)
– CbpA (streptococcal proteins) interact with
glycoconjugate receptors of phosphorylcholine with
platelet activating factor (PAF) on the eukaryotic cells
promote endocytosis and crossing the blood brain
barrier [Radin et al. 2005; Orihuela et al. 2004; Ring et
al. 1998; Cundell et al. 1995]
– Meningococci’s PilC1 adhesin interacts with CD46
and the outer membrane protein connects to
vitronectin and integrins [Unkmeir et al. 2002;
Kallstrom et al. 1997].
8. PATHOGENESIS
• Inflammatory Response
– Inflammatory activation of endothelial cells
seems to be a prerequisite for bacterial invasion
but also results in the regulation of adhesion
molecules as ICAM-I
– These molecules promote the multistep process of
leukocyte invasion
– Leukocytes, in particular the presence of
granulocytes in the CSF are the diagnostic
hallmark of meningitis
9. PATHOGENESIS
• Neuronal damage
– Up to 50% of survivors of bacterial meningitis
suffer from disabling neuropsychological deficits
– Neuronal damage in meningitis is clearly multi-factorial,
involving bacterial toxins, cytotoxic
products of immune competent cells, and indi-rect
pathology secondary to intracranial compli-cations
10. PATHOGENESIS
• Early inflammatory response and bacterial
invasion seem to progress in parallel and
products of activated leukocytes such as
MMPs [Kieseier et al. 1999] and NO [Koedel et
al. 1995] and others contribute to early
damage of the blood brain and blood CSF
barrier. Once bacteria have entered the
subarachnoidal space, they replicate, undergo
autolysis and cause further inflammation.
11. PATHOGENESIS
• The hippocampus seems to be the most
vulnerable area of the brain [Nau et al. 1999a;
van Wees et al. 1990].
• Neuronal loss translates into hippocampal
atrophy and has been reported on MRI scans
in survivors of bacterial meningitis [Free et al.
1996].
12. PATHOGENESIS
• Neuronal damage in meningitis is clearly multifactorial, involving
bacterial toxins, cytotoxic products of immune competent cells,
and indirect pathology secondary to intracranial complications
(Figure 1).
• In the case of S. pneumoniae, the pathogen associated with the
highest frequency of neuronal damage, two major toxins have been
identified, H2O2 and pneumolysin, a pore-forming cytolysin.
• In experimental meningitis induced by toxin-deficient
pneumococcal mutants, neuronal damage was reduced by 50%
compared to wild-type bacteria [Braun et al. 2002].
• The proof of direct bacterial toxicity underlines the critical
importance of rapid antibiotic elimination of living bacteria and
their metabolism. In insufficiently treated patients or resistant
bacteria toxic activity may be significantly prolonged and harm
neuronal functions. Mechanistically, these toxins seem to cause
programmed death of neurons and microglia by inducing rapid
mitochondrial damage.
13. Figure 1. Two major routes
involving bacterial toxins and
cytotoxic products of the
inflammatory response lead to
intracranial complications and
brain damage. Peptidoglycan (PG),
bacterial lipopeptide (LP), lipopo-lysaccharide
(LPS), apoptosis
inducing factor (AIF), intracranial
pressure (ICP).
14. Clinical features and diagnosis
• Early clinical features of bacterial meningitis
are nonspecific
– Fever
– malaise and headache
– meningismus (neck stiffness),
– Photophobia
– phonophobia and vomiting
15. Clinical features and diagnosis
• Headache and meningismus indicate
inflammatory activation of the trigeminal
sensory nerve fibers in the meninges
• Neck stiffness and altered mental state is
present in less than 50% of adults with proven
bacterial meningitis
16. Laboratory tests
• The key to the diagnosis in the CSF by
Gramstaining or a positive bacterial culture
• Detection rates in the CSF may be as high as
90%, while about 50% positive results are
observed in blood cultures
• Polymerase chain reaction (PCR) attempted
if microscopic and cultural identification of the
pathogen
17. Laboratory tests
• The CSF in bacterial meningitis
– White blood cell count (>500 cells/ml) with
predominant neutrophils and a strongly elevated
protein (>1 g/l)
– Increased lactate (>0.3 g/l) and decreased glucose
CSF/blood ratio (<0.4) acute bacterial meningitis
– Use of urine dipsticks for semi quantitive
detection of glucose and leukocyte concentrations
in the CSF
18. CT
• A cranial CT provides information concerning
intracranial complications such as brain
edema, hydrocephalus and infarcts.
• Bone window imaging identifies
parameningeal foci such as sinusitis,
mastoiditis or odontogenic abscess.
• Local infections are especially frequent in
pneumococcal meningitis and may require
surgical treatment.
19. CT
• The risk of cerebral herniation due to raised
intracranial pressure.
• Patients who present with focal neurological
deficits or seizures CT before lumbar
puncture.
• A normal CT does not rule out intracranial
hypertension and a residual risk of herniation
20. Treatment
• Immediate antibiotic therapy is imperative and
must not be postponed by diagnostic delays
• Prehospital antibiotic treatment is advised in
cases of suspected meningococcal disease
• Prior to treatment, a blood culture should be
obtained
• Since microbiological identification of the
pathogen is not immediately available, the initial
choice of antibiotics is usually empirical
21. Treatment
• Cerebral imaging and repeat lumbar puncture
should be considered in patients who fail to
improve clinically after 48 h of treatment to
assess antibiotic failure.
22.
23. Corticosteroids
• Corticosteroids reduce brain edema,
intracranial hypertension and meningeal
inflammation in experimental models of
bacterial meningitis
• “The first steroid dose should be administered 10-
20 min before initiating antibiotic treatment”
• Delayed treatment is not beneficial as
dexamethasone does not reverse existing brain
edema or intracranial hypertension in later stages
of meningitis
24. Other symptomatic therapy
• Severe headache analgesic, often including
opioids.
• Antiepileptic treatment is indicated if seizures
occur (prophylactic treatment is not
recommended)