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CIP2A as a Potential Stratication Marker and Target for Tumor...
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15
CA125 AS A MARKER
FOR THE FOLLOW-UP OF
RELAPSING
POLYSIEROSITIS: A CASE
REPORT
Davide Onofrio Fontana1, Claudio Pedone
Incalzi
1
2
3
Keywords: Peritoneal; Secretion; Malignant; Mucoproteins; Rheumatoid
1,2,3
Area di Geriatria, Policlinico Universitario Campus Bio-Medico, Roma, Italy
Fondazione “Alberto Sordi”, Roma, Italy
Fondazione “San Raffaele - Cittadella della Carità”, Taranto, Italy
1,2
, and Raffaele Antonelli
INTRODUCTION
Ca125 is a well-known marker of many malignant and nonmalignant
diseases the majority of which are characterized by serosal involvement
[1]. Mesothelial secretion of Ca125 rather than direct production by the
neoplastic or inflammatory cells seems to underlie this phenomenon
[2]. Thus, Ca125 qualifies as a marker of serosal, either peritoneal or
pleural, involvement. Not surprisingly, rising levels of Ca125 have been
262
reported to characterize recurrent polyserositis in the context of familiar
Mediterranean fever or systemic lupus erythematous [3]. In these cases it
was observed an increase in Ca125 concentration in patients with active
disease, but Ca125 has not been used as marker of exacerbations.
were heralded by increased Ca125 serum levels, making thus the
periodical and on demand measurement of Ca125 a valuable means for a
preclinical diagnosis of the recurrence.
Advances in Molecular Diagnostics
We report a case of recurrent polyserositis in which exacerbations
CASE REPORT
In November 2008 a 69 year old lady came to our attention for recurrent
polyserositis. Her clinical history dated back to May 2008, when she
was hospitalized elsewhere for fever, abdominal tension and dyspnea.
Erythrocyte sedimentation rate was 23 mm/h, ferritin 341 mg/dl (normal
values [n.v.]: 11-307 mg/dl), LDH 542 mg/dl ( 0-250 mg/dl), GGT 113
mg/dlU/l (n.v. 12-48 U/l), total bilirubin 2.3 mg/dl (n.v. 0.3-1 mg/dl),
indirect bilirubin 1.8 mg/dl (0-0.4 mg/dl), Ca125 57 mg/dlU/ml (n.v.
0-35 U/ml). Mucoproteins were 187 mg/24H (n.v. 0-6 mg/dl), D-dimer
2338 mg/dl (n.v<259 mg/dl). The HbsAg and HbsAb, HBe Ab, and
HBcAb (IgG) were positive, as were the HAVAb IgG. Antitoxoplasm
and anti-citomegalovirus IgG were 5.1 UI/ml (n.v.<12 UI/ml) and 246.7
UI/ml (n.v.<14 UI/ml), respectively, the Widal-Wright test was negative.
Serologic tests for ANA, ANCA, rheumatoidfactor and ENA screening
were all negative. The lymphocyte phenotype showed CD4 1341 cells/
mm3 (n.v. 700-1100/mmc), CD4/CD8 3.2 (n.v.: 1-1.5). A CT scan showed
pulmonary consolidation, pleural and pericardium effusion, ascitic fluid
and a hepatic nodular lesion in the VII segment having a diameter of 17
mm. A tentative diagnosis 3 of pneumonia and polyserositis was made
and levoxacin 500 mg, furosemide 50 mg and prednisone 8 mg prescribed
with remission of symptoms.
In September 2008, after discontinuation of prednisone, she had
ascites and Ca125 rose to 122 mg/dl. A MNR of the abdomen showed
nodular aspect of both annexes. She underwent bilateral annessiectomy
and was treated with corticosteroid therapy. The histological examination
showed reactive mesenchymal cells and few lymphocites in the ascitic
uid, but normal ovaries and fallopian tubes. In November 2008 a biopsy
Ca125 as a Marker for the Follow-up of Relapsing Polysierositis: A...
263
of the hepatic nodular lesion showed chronic hepatitis with mild portal and
intralobular focal activity interface; intralobular accumulation of nely
granular brown pigment in the cytoplasm of perivenous hepatocytes,
groups of histiocytes containing ceroid pigment, outbreaks of hepatocyte
degeneration with cytoplasmic ballooning. Immunohistochemistry
showed positivity for HBsAg and negative for HBcAg Laboratory
exams showed negative quantiferon and absence of antibodies against
mitochondria.
In 2009, pleural and peritoneal effusions relapsed again, with observed
values of Ca125 of 961 U/ml. A genetic study did not disclose MEFV
mutation consistent with familial Mediterranean fever. The diagnosis
of recurrent polyserositis was eventually conrmed and treatment with
methylprednisolone 24 mg started and, then, tapered gradually over 3
months.
Two months after steroid discontinuation, a new relapse occurred
and responded well to a new course of steroids. Afterwards, the patients
was carefully monitored for relapsing pleural or peritoneal effusion by
recording the weight, and a course of corticosteroid was administered at
rst signs of relapses, which usually were abdominal “fullness”, dyspnea,
edema and low grade fever. Later on, Ca125 was measured every three
months, and prednisone was started when this marker at least doubled
with regard to the last basal value, which occurred three times during
one years, preventing thus the new onset of symptoms. This strategy has
proved effective so far, although in the last couple of years the frequency
of exacerbations has increased, with only about two weeks free of
symptoms before a new treatment course is needed.
This case report conrms that Ca125 may be an indicator of the activity
of serositis [4]. However, we add to the current knowledge by showing
that exacerbations of recurrent polyserositis could be prevented and the
related needs of steroids decreased by measuring Ca125 periodically and
in the event of alarming symptoms such as feeling of rising abdominal
tension and fatigue. The early intervention allowed to prevent or abort
the exacerbation through a shorter course and lower cumulative dose of
steroids. Furthermore, it prevented major symptoms such as abdominal
pain, leg oedema and dyspnoea.
Interestingly, Ca125 increase also preceded the rise in inammatory
markers, as if activation of mesothelial cells were the rst step of the
264
exacerbation. Obviously, the timing of Ca125 monitoring was tailored
to our patient and might not be the most appropriate for another patient.
use this early diagnostic strategy.
related side effects. This is especially true in patients, such as ours, with
very limited range of activity and ensuing greater risk of osteoporosis,
sarcopenia and insulin resistance.
cannot exclude that Ca125 serum levels to some extent uctuate. In this
event, the risk exists that a spontaneous uctuation and not an impending
exacerbation accounts for increasing Ca125. Thus, a better knowledge
of the dynamic of Ca125 would allow optimize the Ca125 based follow
up strategy. Nevertheless, it is clear that in our patient monitoring Ca125
could improve the health status and reduce the use of steroids.
impending exacerbations of polyserositis at a preclinical stage and to
guide the therapy accordingly. Experience is needed to translate a single,
yet well documented, case into rules of general interest.
Advances in Molecular Diagnostics
Thus, a careful scrutiny of clinical history is mandatory to correctly
This steroid sparing strategy is also important to prevent steroid
A note of caution in considering this case report is needed because we
In conclusion, Ca125 might be an useful diagnostic tool to diagnose
REFERENCES
1. Miralles C, Orea M, España P, Provencio M, Sánchez A, Cantos B
(2003) et all. Cancer antigen 125 associated with multiple benign
and malignant pathologies. Ann Surg Oncol 10:150-154.
2. Zeillemaker AM, Verbrugh HA, Hoynck van Papendrecht AA,
Leguit P. (1994)CA 125 secretion by peritoneal mesothelial cells. J
Clin Pathol 47:263-265.
3. Moncayo R, Moncayo H. (1991)Serum levels of CA 125 are
elevated in patients with active systemic lupus erythematosus.
Obstet Gynecol 77:932-934.
4. M Funauchi, S Ikoma, H Yu, M Sugiyama (2000) A case of
progressive systemic sclerosis complicated by massive pleural
effusion with elevated CA125. Lupus 9: 382-385
16
MOLECULAR DOCKING TO
TEST FOR EFFICACY OF
PORPHYRIN COMPOUNDS
TO CURE ALZHEIMERS
DISEASE
Nadeem Kizilbash1 and Majed Alrowaili
1
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences,
Northern Border University, Arar-91431, Saudi Arabia
2
Department of Surgery, Faculty of Medicine, Northern Border University, Saudi Arabia
2
ABSTRACT
The cure for Alzheimer’s disease involves searching for candidate
compounds that can act as inhibitors for Acetylcholinesterase (AChE)
enzyme. Regional cerebral blood flow can be increased in patients
with Alzheimer’s disease by Acetylcholinesterase inhibitors. In this
regard, Tetraphenylporphinesulfonate (TPPS), 5,10,15,20-Tetrakis
(4-sulfonatophenyl) porphyrinato Iron(III) Chloride (FeTPPS) and
5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinatoIron(III) nitrosyl
Chloride (FeNOTPPS) were investigated as candidate compounds
for inhibition of Acteylcholinesterase of Drosophila melanogaster
(DmAChE) by use of Molecular Docking. FeNOTPPS was found to
form the most stable complex with DmAChE.
266
Advances in Molecular Diagnostics
INTRODUCTION
Alzheimer’s disease is a progressive neurodegenerative disorder.
Brain regions that are associated with higher mental functions, such
as the neocortex and hippocampus, are those affected by the disease
[1]. The “Cholinergic Hypothesis” for Alzheimer’s disease proposes
that degeneration of cholinergic neurons in the basal forebrain and the
associated loss of cholinergic neurotransmission in the cerebral cortex
and other areas contribute significantly to the deterioration in cognitive
function seen in patients with Alzheimer’s disease [2] (Figure 1).
Figure 1: Proposed neurochemical changes in Alzheimer’s disease.
Acetylcholinesterase enzyme (AChE) is bound to cellular membranes
of excitable tissues at cholinergic synaptic junctions. It catalyzes the
hydrolysis of Acetylcholine neurotransmitter present in the brain [3].
The structure of AChE is a 12-stranded mixed β-sheet surrounded by 14
α- helices. There is a catalytic triad present in the active-site gorge of the
Acteylcholinesterase enzyme of Drosophila melanogaster (DmAChE)
which consists of three amino acids, namely Ser238, His440 and Glu367
(Figure 2).
Figure 2: Schematic representation of the sites in DmAChE. The catalytic triad
in the Acyl Binding Pocket consists of three amino acids, Ser238, His440 and
Glu367.