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Egyptian police fired volleys of tear gas at protesters in several provinces, as thousands took to the streets to demand Islamist President Mohamed Morsi fulfill the goals of the revolt that brought him to power.
Protesters lobbed petrol bombs and set off fireworks, as security vans charged towards demonstrators who fled down the large avenue flanking the presidential palace in Cairo.
Clashes also erupted in several cities and towns in the Nile Delta province of Gharbiya, where the health ministry said 28 people had been injured, suffering mainly from tear gas inhalation.
In the Mediterranean city of Alexandria, five people were hurt in sporadic clashes between police and protesters.
The confrontations came after a day that saw thousands take to the streets across Egypt after opposition groups called "Friday of dignity" rallies.
In recent months, Egypt has witnessed regular, often bloody, protests against Morsi who is accused of betraying the revolution that toppled Hosni Mubarak.
Opponents have accused him of using his power to promote the interests of his Muslim Brotherhood, long banned under his predecessor.
The country has been deeply divided between Morsi's mainly Islamist supporters and an opposition of liberals, leftists, Christians but also deeply religious Muslims calling for rights and the separation of religion and state.
Shortly after Muslim noon prayers, marchers set off from several locations in Cairo to Tahrir Square and the presidential palace, banging on drums, waving flags and clapping in unison.
"The people want the downfall of the regime," the protesters chanted while others slammed interior ministry officials as "thugs".
In Tahrir, several thousand protesters carried aloft a huge Egyptian flag as they listened to speeches and music from the stage.
Several hundred protesters also gathered outside the presidential palace chanting "Freedom, where are you? Brotherhood rule stands between us," in reference to the Muslim Brotherhood movement from which Morsi hails.
The protests come after several incidents of police violence last week that caused public outrage and sparked angry demonstrations.
Protests against the Islamist president also took place after the weekly Friday Muslim main prayers in several of Egypt's 27 provinces.
In the Nile Delta city of Kafr el-Sheikh, police fired tear gas to disperse a crowd outside a government building, as protesters hurled stones at the security forces, the official MENA news agency reported.
In Tanta, police clashed with protesters who tried to break into the municipal council building, MENA added.
Thirty-eight opposition parties and movements had joined together to call for the rallies, demanding a new unity government, amendments to the Islamist-drafted constitution and guarantees that the independence of the judiciary be maintained.
Earlier this week, the death of a pro-democracy activist following days in police custody sparked fury and reignited calls for police reform -- a key demand of the uprising that toppled Mubarak in 2011.
His death came just days after footage was aired live on television of a man stripped naked and beaten by riot police during demonstrations near the presidential palace.
The two incidents confronted Morsi with uncomfortable parallels with the old regime.
Friday's protests come just days after clerics issued fatwas to justify killing opposition leaders.
Radical cleric Mahmud Shaaban, a professor at Sunni Islam's main seat of learning Al-Azhar, gave the green light to kill opposition leaders including former UN nuclear watchdog chief Mohamed ElBaradei and ex-presidential candidate Hamdeen Sabbahi, during a talk show on a satellite channel.
Another hardline cleric, Wagdi Ghoneim, also called on Muslims to "kill the thugs, criminals, and thieves who burn the country," state media reported.
Security was stepped up outside the homes of ElBaradei and Sabbahi ahead of the protests, witnesses told AFP, following orders from the interior minister.
The presidency condemned the fatwas as "terrorism".
"Some are promoting and inciting political violence while others who claim to speak in the name of religion are permitting ‘killing’ based on political differences and this is terrorism," the presidency said.